"RB1" redirects here. For the automobile, see Red Bull RB1.
| Retinoblastoma 1 |
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PDB rendering based on 1ad6.
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| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
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1AD6, 1GH6, 1GUX, 1H25, 1N4M, 1O9K, 1PJM, 2AZE, 2QDJ, 2R7G, 3N5U, 3POM, 4CRI, 4ELJ, 4ELL
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| Identifiers |
| Symbols |
RB1 ; OSRC; PPP1R130; RB; p105-Rb; pRb; pp110 |
| External IDs |
OMIM: 614041 MGI: 97874 HomoloGene: 272 ChEMBL: 5288 GeneCards: RB1 Gene |
| Gene ontology |
| Molecular function |
• core promoter binding
• RNA polymerase II activating transcription factor binding
• DNA binding
• sequence-specific DNA binding transcription factor activity
• transcription coactivator activity
• protein binding
• transcription factor binding
• kinase binding
• ubiquitin protein ligase binding
• identical protein binding
• androgen receptor binding
• phosphoprotein binding
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| Cellular component |
• chromatin
• nucleus
• nucleoplasm
• spindle
• SWI/SNF complex
• PML body
• Rb-E2F complex
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| Biological process |
• cell cycle checkpoint
• G1/S transition of mitotic cell cycle
• regulation of transcription involved in G1/S transition of mitotic cell cycle
• mitotic cell cycle
• chromatin remodeling
• transcription, DNA-templated
• negative regulation of protein kinase activity
• cell cycle arrest
• negative regulation of transcription from RNA polymerase II promoter during mitosis
• mitotic cell cycle checkpoint
• Ras protein signal transduction
• regulation of mitotic cell cycle
• viral process
• androgen receptor signaling pathway
• sister chromatid biorientation
• neuron projection development
• maintenance of mitotic sister chromatid cohesion
• glial cell apoptotic process
• skeletal muscle cell differentiation
• neuron maturation
• enucleate erythrocyte differentiation
• negative regulation of sequence-specific DNA binding transcription factor activity
• regulation of lipid kinase activity
• myoblast differentiation
• positive regulation of macrophage differentiation
• positive regulation of mitotic metaphase/anaphase transition
• negative regulation of smoothened signaling pathway
• negative regulation of transcription, DNA-templated
• positive regulation of transcription, DNA-templated
• positive regulation of transcription from RNA polymerase II promoter
• digestive tract development
• cell morphogenesis involved in neuron differentiation
• negative regulation of epithelial cell proliferation
• striated muscle cell differentiation
• cell division
• neuron apoptotic process
• protein localization to chromosome, centromeric region
• cellular response to xenobiotic stimulus
• regulation of cohesin localization to chromatin
• negative regulation of transcription involved in G1/S transition of mitotic cell cycle
• regulation of centromere complex assembly
• hepatocyte apoptotic process
• negative regulation of G1/S transition of mitotic cell cycle
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| Sources: Amigo / QuickGO |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
| Entrez |
5925 |
19645 |
| Ensembl |
ENSG00000139687 |
ENSMUSG00000022105 |
| UniProt |
P06400 |
P13405 |
| RefSeq (mRNA) |
NM_000321 |
NM_009029 |
| RefSeq (protein) |
NP_000312 |
NP_033055 |
| Location (UCSC) |
Chr 13:
48.3 – 48.48 Mb |
Chr 14:
73.18 – 73.33 Mb |
| PubMed search |
[1] |
[2] |
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The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated RB or RB1) is a tumor suppressor protein that is dysfunctional in several major cancers.[1] One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. When the cell is ready to divide, pRb is phosphorylated, becomes inactive and allows cell cycle progression. It is also a recruiter of several chromatin remodeling enzymes such as methylases and acetylases.[2]
Rb belongs to the pocket protein family, whose members have a pocket for the functional binding of other proteins.[3][4] Should an oncogenic protein, such as those produced by cells infected by high-risk types of human papillomaviruses, bind and inactivate pRb, this can lead to cancer.
Contents
- 1 Name and genetics
- 2 Cell cycle suppression
- 3 Detection
- 4 Activation and inactivation
- 5 Regeneration
- 6 Interactions
- 7 See also
- 8 References
- 9 Further reading
- 10 External links
Name and genetics
In humans, the protein is encoded by the RB1 gene located on 13q14.1-q14.2. If both alleles of this gene are mutated early in life, the protein is inactivated and results in development of retinoblastoma cancer, hence the name Rb. Retinal cells are not sloughed off or replaced, and are subjected to high levels of mutagenic UV radiation, and thus most pRB knock-outs occur in retinal tissue (but it's also been documented in certain skin cancers in patients from New Zealand where the amount of UV radiation is significantly higher).
Two forms of retinoblastoma were noticed: a bilateral, familial form and a unilateral, sporadic form. Sufferers of the former were 6 times more likely to develop other types of cancer later in life.[5] This highlighted the fact that mutated Rb could be inherited and lent support to the two-hit hypothesis. This states that only one working allele of a tumour suppressor gene is necessary for its function (the mutated gene is recessive), and so both need to be mutated before the cancer phenotype will appear. In the familial form, a mutated allele is inherited along with a normal allele. In this case, should a cell sustain only one mutation in the other RB gene, all Rb in that cell would be ineffective at inhibiting cell cycle progression, allowing cells to divide uncontrollably and eventually become cancerous. Furthermore, as one allele is already mutated in all other somatic cells, the future incidence of cancers in these individuals is observed with linear kinetics.[6] The working allele need not undergo a mutation per se, as loss of heterozygosity (LOH) is frequently observed in such tumours.
However, in the sporadic form, both alleles would need to sustain a mutation before the cell can become cancerous. This explains why sufferers of sporadic retinoblastoma are not at increased risk of cancers later in life, as both alleles are functional in all their other cells. Future cancer incidence in sporadic Rb cases is observed with polynomial kinetics, not exactly quadratic as expected because the first mutation must arise through normal mechanisms, and then can be duplicated by LOH to result in a tumour progenitor.
RB1 orthologs[7] have also been identified in most mammals for which complete genome data are available.
RB/E2F-family proteins repression transcription.[8]
Cell cycle suppression
Rb restricts the cell's ability to replicate DNA by preventing its progression from the G1 (first gap phase) to S (synthesis phase) phase of the cell division cycle.[9] Rb binds and inhibits transcription factors of the E2F family, which are composed of dimers of an E2F protein and a dimerization partner (DP) protein.[10] The transcription activating complexes of E2 promoter-binding–protein-dimerization partners (E2F-DP) can push a cell into S phase.[11][12][13][14][15] As long as E2F-DP is inactivated, the cell remains stalled in the G1 phase. When Rb is bound to E2F, the complex acts as a growth suppressor and prevents progression through the cell cycle.[4] The Rb-E2F/DP complex also attracts a histone deacetylase (HDAC) protein to the chromatin, reducing transcription of S phase promoting factors, further suppressing DNA synthesis.
Detection
Several methods for detecting the RB1 gene mutations have been developed[16] including a method that can detect large deletions that correlate with advanced stage retinoblastoma.[17]
Activation and inactivation
See also: cyclin-dependent kinase and DREAM complex
Rb is phosphorylated to pRb by certain cyclin-dependent kinases (CDKs). pRb is described as being hyperphosphorylated and when in this state, it is unable to complex E2F and therefore, unable to restrict progression from the G1 phase to the S phase of the cell cycle. During the M-to-G1 transition, pRb is progressively dephosphorylated by PP1, returning to its growth-suppressive hypophosphorylated state Rb .[4][18]
When it is time for a cell to enter S phase, complexes of cyclin-dependent kinases (CDK) and cyclins phosphorylate Rb to pRb, inhibiting its activity.[3][4][19][20] The initial phosphorylation is performed by Cyclin D/CDK4/CDK6 and followed by additional phosphorylation by Cyclin E/CDK2. pRb remains phosphorylated throughout S, G2 and M phases.[4]
Phosphorylation of Rb allows E2F-DP to dissociate from pRb and become active.[4][12][19] When E2F is free it activates factors like cyclins (e.g. Cyclin E and A), which push the cell through the cell cycle by activating cyclin-dependent kinases, and a molecule called proliferating cell nuclear antigen, or PCNA, which speeds DNA replication and repair by helping to attach polymerase to DNA.[11][14][19]
Rb family proteins are components of the DREAM complex (also named LINC complex), which is composed of LIN9, LIN54, LIN37, MYBL2, RBL1, RBL2, RBBP4, TFDP1, TFDP2, E2F4 and E2F5. There is a testis-specific version of the complex, where LIN54, MYBL2 and RBBP4 are replaced by MTL5, MYBL1 and RBBP7, respectively. In Drosophila both DREAM versions also exist, the components being mip130 (lin9 homolog, replaced by aly in testes), mip120 (lin54 homolog, replaced by tomb in testes), and Myb, Caf1p55, DP, Mip40, E2F2, Rbf and Rbf2. The DREAM complex exists in quiescent cells in association with MuvB (consisting of HDAC1 or HDAC2, LIN52 and L3mbtl1, L3mbtl3 or L3mbtl4) where it represses cell cycle-dependent genes. DREAM dissociates in S phase from MuvB and gets recruited by MYB.
Regeneration
Cochlea
The retinoblastoma protein is involved in the growth and development of mammalian hair cells of the cochlea, and appears to be related to the cells' inability to regenerate. Embryonic hair cells require Rb, among other important proteins, to exit the cell-cycle and stop dividing, which allows maturation of the auditory system. Once wild-type mammals have reached adulthood, their cochlear hair cells become incapable of proliferation. In studies where the gene for Rb is deleted in mice cochlea, hair cells continue to proliferate in early adulthood. Though this may seem to be a positive development, Rb-knockdown mice tend to develop severe hearing loss due to degeneration of the organ of Corti. For this reason, Rb seems to be instrumental for completing the development of mammalian hair cells and keeping them alive.[21][22] However, it is clear that without Rb, hair cells have the ability to proliferate, which is why Rb is known as a tumor suppressor. Temporarily and precisely turning off Rb in adult mammals with damaged hair cells may lead to propagation and therefore successful regeneration. Suppressing function of the retinoblastoma protein in the adult rat cochlea has been found to cause proliferation of supporting cells and hair cells. Rb can be downregulated by activating the sonic hedgehog pathway, which phosphorylates the proteins and reduces gene transcription.[23]
Neurons
Disrupting Rb expression in vitro, either by gene deletion or knockdown of Rb short interfering RNA, causes dendrites to branch out farther. In addition, Schwann cells, which provide essential support for the survival of neurons, travel with the neurites, extending farther than normal. The inhibition of Rb supports the continued growth of nerve cells.[24]
Interactions
Retinoblastoma protein has been shown to interact with:
- Abl gene[25][26]
- Androgen receptor[27][28]
- Apoptosis-antagonizing transcription factor[29][30]
- ARID4A[31]
- Aryl hydrocarbon receptor[32]
- BRCA1[33][34][35]
- BRF1[36][37]
- C-jun[38]
- C-Raf[39][40]
- CDK9[41]
- CUTL1[42]
- Cyclin A1[43]
- Cyclin D1[44][45]
- Cyclin T2[41]
- DNMT1[46]
- E2F1[47][48][49][50][51][52][53]
- E2F2,[54]
- E4F1[50]
- EID1[55][56]
- ENC1[57]
- FRK[58]
- HBP1[59]
- HDAC1[31][60][61][62][63][64][65]
- HDAC3[31][66]
- Histone deacetylase 2[31]
- Insulin[67]
- JARID1A[68][69]
- LIN9[70]
- MCM7[71]
- MORF4L1[48][72]
- MRFAP1,[48][72]
- MyoD[73][74]
- NCOA6[75]
- PA2G4[76]
- Peroxisome proliferator-activated receptor gamma[66]
- PIK3R3[77]
- Plasminogen activator inhibitor-2[78]
- Polymerase (DNA directed), alpha 1[79]
- PRDM2[80]
- PRKRA[81]
- Prohibitin[40][82]
- Promyelocytic leukemia protein[83]
- RBBP4[47][84]
- RBBP7[35][84]
- RBBP8[60][85]
- RBBP9[86]
- SNAPC1[87]
- SKP2[88][89]
- SNAPC3[87]
- SNW1[90]
- SUV39H1[91][92]
- TAF1[44][93][94][95]
- THOC1[96]
- TRAP1[97]
- TRIP11[98]
- UBTF[99]
- USP4.[100]
Overview of signal transduction pathways involved in apoptosis.
See also
- p53 - involved in the DNA repair support function of pRb
- Transcription coregulator
- Retinoblastoma
References
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- ^ Wu CL, Zukerberg LR, Ngwu C, Harlow E, Lees JA (May 1995). "In vivo association of E2F and DP family proteins". Mol. Cell. Biol. 15 (5): 2536–46. PMC 230484. PMID 7739537.
- ^ Taniura H, Taniguchi N, Hara M, Yoshikawa K (January 1998). "Necdin, a postmitotic neuron-specific growth suppressor, interacts with viral transforming proteins and cellular transcription factor E2F1". J. Biol. Chem. 273 (2): 720–8. doi:10.1074/jbc.273.2.720. PMID 9422723.
- ^ Lee C, Chang JH, Lee HS, Cho Y (December 2002). "Structural basis for the recognition of the E2F transactivation domain by the retinoblastoma tumor suppressor". Genes Dev. 16 (24): 3199–212. doi:10.1101/gad.1046102. PMC 187509. PMID 12502741.
- ^ Miyake S, Sellers WR, Safran M, Li X, Zhao W, Grossman SR, Gan J, DeCaprio JA, Adams PD, Kaelin WG (December 2000). "Cells Degrade a Novel Inhibitor of Differentiation with E1A-Like Properties upon Exiting the Cell Cycle". Mol. Cell. Biol. 20 (23): 8889–902. doi:10.1128/MCB.20.23.8889-8902.2000. PMC 86544. PMID 11073989.
- ^ MacLellan WR, Xiao G, Abdellatif M, Schneider MD (December 2000). "A Novel Rb- and p300-Binding Protein Inhibits Transactivation by MyoD". Mol. Cell. Biol. 20 (23): 8903–15. doi:10.1128/MCB.20.23.8903-8915.2000. PMC 86545. PMID 11073990.
- ^ Kim TA, Lim J, Ota S, Raja S, Rogers R, Rivnay B, Avraham H, Avraham S (May 1998). "NRP/B, a Novel Nuclear Matrix Protein, Associates With p110RB and Is Involved in Neuronal Differentiation". J. Cell Biol. 141 (3): 553–66. doi:10.1083/jcb.141.3.553. PMC 2132755. PMID 9566959.
- ^ Craven RJ, Cance WG, Liu ET (September 1995). "The nuclear tyrosine kinase Rak associates with the retinoblastoma protein pRb". Cancer Res. 55 (18): 3969–72. PMID 7664264.
- ^ Lavender P, Vandel L, Bannister AJ, Kouzarides T (June 1997). "The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A". Oncogene 14 (22): 2721–8. doi:10.1038/sj.onc.1201243. PMID 9178770.
- ^ a b Dick FA, Sailhamer E, Dyson NJ (May 2000). "Mutagenesis of the pRB Pocket Reveals that Cell Cycle Arrest Functions Are Separable from Binding to Viral Oncoproteins". Mol. Cell. Biol. 20 (10): 3715–27. doi:10.1128/MCB.20.10.3715-3727.2000. PMC 85672. PMID 10779361.
- ^ Fuks F, Burgers WA, Brehm A, Hughes-Davies L, Kouzarides T (January 2000). "DNA methyltransferase Dnmt1 associates with histone deacetylase activity". Nat. Genet. 24 (1): 88–91. doi:10.1038/71750. PMID 10615135.
- ^ Puri PL, Iezzi S, Stiegler P, Chen TT, Schiltz RL, Muscat GE, Giordano A, Kedes L, Wang JY, Sartorelli V (October 2001). "Class I histone deacetylases sequentially interact with MyoD and pRb during skeletal myogenesis". Mol. Cell 8 (4): 885–97. doi:10.1016/S1097-2765(01)00373-2. PMID 11684023.
- ^ Wang S, Fusaro G, Padmanabhan J, Chellappan SP (December 2002). "Prohibitin co-localizes with Rb in the nucleus and recruits N-CoR and HDAC1 for transcriptional repression". Oncogene 21 (55): 8388–96. doi:10.1038/sj.onc.1205944. PMID 12466959.
- ^ Luo RX, Postigo AA, Dean DC (February 1998). "Rb interacts with histone deacetylase to repress transcription". Cell 92 (4): 463–73. doi:10.1016/S0092-8674(00)80940-X. PMID 9491888.
- ^ Ferreira R, Magnaghi-Jaulin L, Robin P, Harel-Bellan A, Trouche D (September 1998). "The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase". Proc. Natl. Acad. Sci. U.S.A. 95 (18): 10493–8. doi:10.1073/pnas.95.18.10493. PMC 27922. PMID 9724731.
- ^ a b Fajas L, Egler V, Reiter R, Hansen J, Kristiansen K, Debril MB, Miard S, Auwerx J (December 2002). "The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation". Dev. Cell 3 (6): 903–10. doi:10.1016/S1534-5807(02)00360-X. PMID 12479814.
- ^ Radulescu RT, Bellitti MR, Ruvo M, Cassani G, Fassina G (January 1995). "Binding of the LXCXE Insulin Motif to a Hexapeptide Derived from Retinoblastoma Protein". Biochemical and Biophysical Research Communications 206 (1): 97–102. doi:10.1006/bbrc.1995.1014. PMID 7818556.
- ^ Chan SW, Hong W (July 2001). "Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription". J. Biol. Chem. 276 (30): 28402–12. doi:10.1074/jbc.M100313200. PMID 11358960.
- ^ Kim YW, Otterson GA, Kratzke RA, Coxon AB, Kaye FJ (November 1994). "Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein". Mol. Cell. Biol. 14 (11): 7256–64. PMC 359260. PMID 7935440.
- ^ Gagrica S, Hauser S, Kolfschoten I, Osterloh L, Agami R, Gaubatz S (November 2004). "Inhibition of oncogenic transformation by mammalian Lin-9, a pRB-associated protein". EMBO J. 23 (23): 4627–38. doi:10.1038/sj.emboj.7600470. PMC 533054. PMID 15538385.
- ^ Sterner JM, Dew-Knight S, Musahl C, Kornbluth S, Horowitz JM (May 1998). "Negative Regulation of DNA Replication by the Retinoblastoma Protein Is Mediated by Its Association with MCM7". Mol. Cell. Biol. 18 (5): 2748–57. PMC 110654. PMID 9566894.
- ^ a b Leung JK, Berube N, Venable S, Ahmed S, Timchenko N, Pereira-Smith OM (October 2001). "MRG15 activates the B-myb promoter through formation of a nuclear complex with the retinoblastoma protein and the novel protein PAM14". J. Biol. Chem. 276 (42): 39171–8. doi:10.1074/jbc.M103435200. PMID 11500496.
- ^ Mal A, Sturniolo M, Schiltz RL, Ghosh MK, Harter ML (April 2001). "A role for histone deacetylase HDAC1 in modulating the transcriptional activity of MyoD: inhibition of the myogenic program". EMBO J. 20 (7): 1739–53. doi:10.1093/emboj/20.7.1739. PMC 145490. PMID 11285237.
- ^ Gu W, Schneider JW, Condorelli G, Kaushal S, Mahdavi V, Nadal-Ginard B (February 1993). "Interaction of myogenic factors and the retinoblastoma protein mediates muscle cell commitment and differentiation". Cell 72 (3): 309–24. doi:10.1016/0092-8674(93)90110-C. PMID 8381715.
- ^ Goo YH, Na SY, Zhang H, Xu J, Hong S, Cheong J, Lee SK, Lee JW (February 2004). "Interactions between activating signal cointegrator-2 and the tumor suppressor retinoblastoma in androgen receptor transactivation". J. Biol. Chem. 279 (8): 7131–5. doi:10.1074/jbc.M312563200. PMID 14645241.
- ^ Xia X, Cheng A, Lessor T, Zhang Y, Hamburger AW (May 2001). "Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb transcriptional regulation". J. Cell. Physiol. 187 (2): 209–17. doi:10.1002/jcp.1075. PMID 11268000.
- ^ Xia X, Cheng A, Akinmade D, Hamburger AW (March 2003). "The N-Terminal 24 Amino Acids of the p55 Gamma Regulatory Subunit of Phosphoinositide 3-Kinase Binds Rb and Induces Cell Cycle Arrest". Mol. Cell. Biol. 23 (5): 1717–25. doi:10.1128/MCB.23.5.1717-1725.2003. PMC 151709. PMID 12588990.
- ^ Darnell GA, Antalis TM, Johnstone RW, Stringer BW, Ogbourne SM, Harrich D, Suhrbier A (September 2003). "Inhibition of Retinoblastoma Protein Degradation by Interaction with the Serpin Plasminogen Activator Inhibitor 2 via a Novel Consensus Motif". Mol. Cell. Biol. 23 (18): 6520–32. doi:10.1128/MCB.23.18.6520-6532.2003. PMC 193706. PMID 12944478.
- ^ Takemura M, Kitagawa T, Izuta S, Wasa J, Takai A, Akiyama T, Yoshida S (November 1997). "Phosphorylated retinoblastoma protein stimulates DNA polymerase alpha". Oncogene 15 (20): 2483–92. doi:10.1038/sj.onc.1201431. PMID 9395244.
- ^ Buyse IM, Shao G, Huang S (May 1995). "The retinoblastoma protein binds to RIZ, a zinc-finger protein that shares an epitope with the adenovirus E1A protein". Proc. Natl. Acad. Sci. U.S.A. 92 (10): 4467–71. doi:10.1073/pnas.92.10.4467. PMC 41965. PMID 7538672.
- ^ Simons A, Melamed-Bessudo C, Wolkowicz R, Sperling J, Sperling R, Eisenbach L, Rotter V (January 1997). "PACT: cloning and characterization of a cellular p53 binding protein that interacts with Rb". Oncogene 14 (2): 145–55. doi:10.1038/sj.onc.1200825. PMID 9010216.
- ^ Wang S, Nath N, Adlam M, Chellappan S (June 1999). "Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function". Oncogene 18 (23): 3501–10. doi:10.1038/sj.onc.1202684. PMID 10376528.
- ^ Alcalay M, Tomassoni L, Colombo E, Stoldt S, Grignani F, Fagioli M, Szekely L, Helin K, Pelicci PG (February 1998). "The Promyelocytic Leukemia Gene Product (PML) Forms Stable Complexes with the Retinoblastoma Protein". Mol. Cell. Biol. 18 (2): 1084–93. PMC 108821. PMID 9448006.
- ^ a b Qian YW, Lee EY (October 1995). "Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast". J. Biol. Chem. 270 (43): 25507–13. doi:10.1074/jbc.270.43.25507. PMID 7503932.
- ^ Fusco C, Reymond A, Zervos AS (August 1998). "Molecular cloning and characterization of a novel retinoblastoma-binding protein". Genomics 51 (3): 351–8. doi:10.1006/geno.1998.5368. PMID 9721205.
- ^ Woitach JT, Zhang M, Niu CH, Thorgeirsson SS (August 1998). "A retinoblastoma-binding protein that affects cell-cycle control and confers transforming ability". Nat. Genet. 19 (4): 371–4. doi:10.1038/1258. PMID 9697699.
- ^ a b Hirsch HA, Gu L, Henry RW (December 2000). "The Retinoblastoma Tumor Suppressor Protein Targets Distinct General Transcription Factors To Regulate RNA Polymerase III Gene Expression". Mol. Cell. Biol. 20 (24): 9182–91. doi:10.1128/MCB.20.24.9182-9191.2000. PMC 102176. PMID 11094070.
- ^ Ji P, Jiang H, Rekhtman K, Bloom J, Ichetovkin M, Pagano M, Zhu L (October 2004). "An Rb-Skp2-p27 pathway mediates acute cell cycle inhibition by Rb and is retained in a partial-penetrance Rb mutant". Mol. Cell 16 (1): 47–58. doi:10.1016/j.molcel.2004.09.029. PMID 15469821.
- ^ Wang H, Bauzon F, Ji P, Xu X, Sun D, Locker J, Sellers RS, Nakayama K, Nakayama KI, Cobrinik D, Zhu L (January 2010). "Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1+/- mice". Nat. Genet. 42 (1): 83–8. doi:10.1038/ng.498. PMC 2990528. PMID 19966802.
- ^ Prathapam T, Kühne C, Banks L (December 2002). "Skip interacts with the retinoblastoma tumor suppressor and inhibits its transcriptional repression activity". Nucleic Acids Res. 30 (23): 5261–8. doi:10.1093/nar/gkf658. PMC 137971. PMID 12466551.
- ^ Nielsen SJ, Schneider R, Bauer UM, Bannister AJ, Morrison A, O'Carroll D, Firestein R, Cleary M, Jenuwein T, Herrera RE, Kouzarides T (August 2001). "Rb targets histone H3 methylation and HP1 to promoters". Nature 412 (6846): 561–5. doi:10.1038/35087620. PMID 11484059.
- ^ Vandel L, Nicolas E, Vaute O, Ferreira R, Ait-Si-Ali S, Trouche D (October 2001). "Transcriptional Repression by the Retinoblastoma Protein through the Recruitment of a Histone Methyltransferase". Mol. Cell. Biol. 21 (19): 6484–94. doi:10.1128/MCB.21.19.6484-6494.2001. PMC 99795. PMID 11533237.
- ^ Shao Z, Ruppert S, Robbins PD (April 1995). "The retinoblastoma-susceptibility gene product binds directly to the human TATA-binding protein-associated factor TAFII250". Proc. Natl. Acad. Sci. U.S.A. 92 (8): 3115–9. doi:10.1073/pnas.92.8.3115. PMC 42115. PMID 7724524.
- ^ Siegert JL, Robbins PD (January 1999). "Rb Inhibits the Intrinsic Kinase Activity of TATA-Binding Protein-Associated Factor TAFII250". Mol. Cell. Biol. 19 (1): 846–54. PMC 83941. PMID 9858607.
- ^ Shao Z, Siegert JL, Ruppert S, Robbins PD (July 1997). "Rb interacts with TAF(II)250/TFIID through multiple domains". Oncogene 15 (4): 385–92. doi:10.1038/sj.onc.1201204. PMID 9242374.
- ^ Durfee T, Mancini MA, Jones D, Elledge SJ, Lee WH (November 1994). "The amino-terminal region of the retinoblastoma gene product binds a novel nuclear matrix protein that co-localizes to centers for RNA processing". J. Cell Biol. 127 (3): 609–22. doi:10.1083/jcb.127.3.609. PMC 2120229. PMID 7525595.
- ^ Chen CF, Chen Y, Dai K, Chen PL, Riley DJ, Lee WH (September 1996). "A new member of the hsp90 family of molecular chaperones interacts with the retinoblastoma protein during mitosis and after heat shock". Mol. Cell. Biol. 16 (9): 4691–9. PMC 231469. PMID 8756626.
- ^ Chang KH, Chen Y, Chen TT, Chou WH, Chen PL, Ma YY, Yang-Feng TL, Leng X, Tsai MJ, O'Malley BW, Lee WH (August 1997). "A thyroid hormone receptor coactivator negatively regulated by the retinoblastoma protein". Proc. Natl. Acad. Sci. U.S.A. 94 (17): 9040–5. doi:10.1073/pnas.94.17.9040. PMC 23019. PMID 9256431.
- ^ Hannan KM, Hannan RD, Smith SD, Jefferson LS, Lun M, Rothblum LI (October 2000). "Rb and p130 regulate RNA polymerase I transcription: Rb disrupts the interaction between UBF and SL-1". Oncogene 19 (43): 4988–99. doi:10.1038/sj.onc.1203875. PMID 11042686.
- ^ Blanchette P, Gilchrist CA, Baker RT, Gray DA (September 2001). "Association of UNP, a ubiquitin-specific protease, with the pocket proteins pRb, p107 and p130". Oncogene 20 (39): 5533–7. doi:10.1038/sj.onc.1204823. PMID 11571651.
Further reading
- Momand J, Wu HH, Dasgupta G (2000). "MDM2—master regulator of the p53 tumor suppressor protein". Gene 242 (1–2): 15–29. doi:10.1016/S0378-1119(99)00487-4. PMID 10721693.
- Zheng L, Lee WH (2003). "Retinoblastoma tumor suppressor and genome stability". Adv. Cancer Res. Advances in Cancer Research 85: 13–50. doi:10.1016/S0065-230X(02)85002-3. ISBN 978-0-12-006685-8. PMID 12374284.
- Classon M, Harlow E (2003). "The retinoblastoma tumour suppressor in development and cancer". Nature Reviews Cancer 2 (12): 910–7. doi:10.1038/nrc950. PMID 12459729.
- Lai H, Ma F, Lai S (2003). "Identification of the novel role of pRB in eye cancer". J. Cell. Biochem. 88 (1): 121–7. doi:10.1002/jcb.10283. PMID 12461781.
- Simin K, Wu H, Lu L, Pinkel D, Albertson D, Cardiff RD, Van Dyke T (2006). "pRb Inactivation in Mammary Cells Reveals Common Mechanisms for Tumor Initiation and Progression in Divergent Epithelia". PLoS Biol. 2 (2): E22. doi:10.1371/journal.pbio.0020022. PMC 340938. PMID 14966529.
- Lohmann DR, Gallie BL (2004). "Retinoblastoma: revisiting the model prototype of inherited cancer". American Journal of Medical Genetics 129 (1): 23–8. doi:10.1002/ajmg.c.30024. PMID 15264269.
- Clemo NK, Arhel NJ, Barnes JD, Baker J, Moorghen M, Packham GK, Paraskeva C, Williams AC (2005). "The role of the retinoblastoma protein (Rb) in the nuclear localization of BAG-1: implications for colorectal tumour cell survival". Biochem. Soc. Trans. 33 (Pt 4): 676–8. doi:10.1042/BST0330676. PMID 16042572.
- Rodríguez-Cruz M, del Prado M, Salcedo M (2006). "[Genomic retinoblastoma perspectives: implications of tumor supressor gene RB1]". Rev. Invest. Clin. 57 (4): 572–81. PMID 16315642.
- Knudsen ES, Knudsen KE (2006). "Retinoblastoma tumor suppressor: where cancer meets the cell cycle". Exp. Biol. Med. (Maywood) 231 (7): 1271–81. PMID 16816134.
External links
- RB1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
- Retinoblastoma genes at the US National Library of Medicine Medical Subject Headings (MeSH)
- GeneReviews/NIH/NCBI/UW entry on Retinoblastoma
- Retinoblastoma Genetics
- Drosophila Retinoblastoma-family protein - The Interactive Fly
- Drosophila Retinoblastoma-family protein 2 - The Interactive Fly
- Evolutionary Homologs Retinoblastoma-family proteins - The Interactive Fly
- There is a diagram of the pRb-E2F interactions here.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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PDB gallery
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1ad6: DOMAIN A OF HUMAN RETINOBLASTOMA TUMOR SUPPRESSOR
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1gh6: RETINOBLASTOMA POCKET COMPLEXED WITH SV40 LARGE T ANTIGEN
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1gux: RB POCKET BOUND TO E7 LXCXE MOTIF
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1o9k: CRYSTAL STRUCTURE OF THE RETINOBLASTOMA TUMOUR SUPPRESSOR PROTEIN BOUND TO E2F PEPTIDE
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2aze: Structure of the Rb C-terminal domain bound to an E2F1-DP1 heterodimer
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Transcription coregulators
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| Coactivators |
- ARA (54, 55, 70)
- BCAS3
- CARM1
- p300-CBP (EP300, CREBBP)
- CRTC (1, 2, 3)
- DRIP/TRAP (MED1 Drip205/Trap220)
- MN1
- PCAF
- PNRC (1, 2)
- PPARGC (1A, 1B)
- TGFB1I1
NCOA1 (SRC-1)
- NCOA2 (GRIP1/SRC-2/TIF2)
- NCOA3 (AIB/SRC-3/TRAM-1)
- NCOA4 (ARA70)
- NCOA5 (CIA)
- NCOA6 (RAP250)
- NCOA7 (ERAP140)
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| Corepressors |
- CTBP (1, 2)
- Hairless homolog
- LCOR
- NRIP1 (RIP140)
- PELP-1
- RCOR1
- Rb
- SIN3A
- SIN3B
- Tripartite motif family TRIM (24, 28, 33)
NCOR1
- NCOR2 (SMRT)
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| ATP-dependent remodeling factors |
- Chromatin Structure Remodeling (RSC) Complex
- SWI/SNF
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Index of genetics
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| Description |
- Gene expression
- DNA
- replication
- cycle
- recombination
- repair
- binding proteins
- Transcription
- factors
- regulators
- nucleic acids
- RNA
- RNA binding proteins
- ribonucleoproteins
- repeated sequence
- modification
- Translation
- ribosome
- modification
- nexins
- Proteins
- domains
- Structure
- primary
- secondary
- tertiary
- quaternary
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| Disease |
- Replication and repair
- Transcription factor
- Transcription
- Translation
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Neoplasm: Tumor suppressor genes/proteins and Oncogenes/Proto-oncogenes
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| Ligand |
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| Receptor |
| Wnt signaling pathway |
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| Hedgehog signaling pathway |
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| TGF beta signaling pathway |
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| Receptor tyrosine kinase |
- ONCO: ErbB/c-ErbB
- c-Met
- c-Ret
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| JAK-STAT signaling pathway |
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| Intracellular signaling P+Ps |
| Wnt signaling pathway |
- ONCO: Beta-catenin
- TSP: APC
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| TGF beta signaling pathway |
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| Akt/PKB signaling pathway |
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| Hippo signaling pathway |
- TSP: Neurofibromin 2/Merlin
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| MAPK/ERK pathway |
- TSP: Neurofibromin 1
- ONCO: c-Ras
- HRAS
- c-Raf
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| Other/unknown |
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| Nucleus |
| Cell cycle |
- TSP: p53
- pRb
- WT1
- p16/p14arf
- ONCO: CDK4
- Cyclin D
- Cyclin E
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| DNA repair/Fanconi |
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| Ubiquitin ligase |
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| Transcription factor |
- TSP: KLF6
- ONCO: AP-1
- c-Myc
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| Mitochondrion |
- Apoptosis inhibitor: SDHB
- SDHD
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| Other/ungrouped |
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Index of neoplasms and cancer
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| Description |
- Tumor suppressing and oncogenes
- Tumor markers
- Carcinogen
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| Disease |
- Neoplasms and cancer
- Symptoms and signs
- Paraneoplastic
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| Treatment |
- Radiotherapy
- Drugs
- Immunotherapy
- intracellular chemotherapeutics
- extracellular chemotherapeutics
- adjuvant detoxification
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