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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/04/20 19:53:06」(JST)

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Thrombospondins are a family of secreted glycoproteins with antiangiogenic functions. Due to their dynamic role within the extracellular matrix they are considered matricellular proteins.^[1] The first member of the family, thrombospondin 1 (THBS1), was discovered in 1971 by Nancy L. Baenziger.^[2]

Types

The thrombospondins (TSP) are a family of multifunctional proteins. The family consists of thrombospondins 1-5 and can be divided into 2 subgroups: A, which contains TSP-1 and -2, and B, which contains TSP-3, -4 and -5 (also designated cartilage oligomeric protein or COMP). TSP-1 and -2 are homotrimers, consisting of three identical subunits, whereas TSP-3, -4 and -5 are homopentamers.

TSP-1 and TSP-2 are produced by immature astrocytes during brain development, which promotes the development of new synapses.^[3]

Thrombospondin 1

Thrombospondin 1 (TSP-1) is encoded by THBS1. It was first isolated from platelets that had been stimulated with thrombin, and so was designated 'thrombin-sensitive protein'.^[2] Since its first recognition, functions for TSP-1 have been found in multiple biological processes including angiogenesis, apoptosis, activation of TGF-beta and Immune regulation. As such, TSP-1 is designated a multifunctional protein.

TSP-1 has multiple receptors, among which CD36, CD47 and integrins are of particular note.

TSP-1 is an antiangiogenic, inhibiting the proliferation and migration of endothelial cells by interactions with CD36 expressed on their surface of these cells. Inhibitory peptides and fragments of TSP1 bind to CD36, leading to the expression of FAS ligand (FasL), which activates its specific, ubiquitous receptor, Fas. This leads to the activation of caspases and apoptosis of the cell. Since tumors overexpressing TSP-1 typically grow slower, exhibit less angiogenesis, and have fewer metastases, TSP1 is an attractive target for cancer treatment. Because TSP1 is extremely large (~120 kDa monomer), not very abundant and exerts multiple actions, its clinical usefulness is questionable. However, small-molecules based on a CD36-binding peptide sequence from TSP1 are being tested. One analog, ABT-510, exhibits potent proapoptotic activity in cultured cells, while clinically it is very well tolerated with therapeutic benefits reported against several malignancies.^[4] ABT-510 is being evaluated in phase II clinical trials for the treatment of several types of cancer.^[5]

Human proteins containing this domain

ADAMTS1; ADAMTS10; ADAMTS12; ADAMTS13; ADAMTS14; ADAMTS15; ADAMTS16; ADAMTS17; ADAMTS18; ADAMTS19; ADAMTS2; ADAMTS20; ADAMTS3; ADAMTS4; ADAMTS5; ADAMTS6; ADAMTS7; ADAMTS8; ADAMTS9; ADAMTSL1; ADAMTSL2; ADAMTSL3; ADAMTSL4; ADAMTSL5; BAI1; BAI2; BAI3; C6; C7; C8A; C8B; C9; C9orf8; C9orf94; CFP; CILP; CILP2; CTGF; CYR61; HMCN1; LIBC; NOV; PAPLN; RSPO1; RSPO3; SEMA5A; SEMA5B; SPON1; SPON2; SSPO; THBS1; THBS2; THSD1; THSD3; THSD7A; THSD7B; UNC5A; UNC5B; UNC5C; UNC5D; WISP1; WISP2; WISP3;

References

^ Morris, Aaron H.; Kyriakides, Themis R. (July 2014). "Matricellular proteins and biomaterials". Matrix Biology 37: 183–191. doi:10.1016/j.matbio.2014.03.002.
^ ^a ^b Baenziger NL, Brodie GN, Majerus PW (January 1971). "A Thrombin-Sensitive Protein of Human Platelet Membranes". Proc. Natl. Acad. Sci. U.S.A. 68 (1): 240–3. doi:10.1073/pnas.68.1.240. PMC: 391203. PMID 5276296.
^ Christopherson KS, Ullian EM, Stokes CC,Mullowney CE, Hell JW, Agah A, Lawler J, Mosher DF, Bornstein P, Barres BA. (2005). "Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis". Cell 120 (3): 421–33. doi:10.1016/j.cell.2004.12.020. PMID 15707899.
^ Haviv F, Bradley MF, Kalvin DM, et al. (April 2005). "Thrombospondin-1 mimetic peptide inhibitors of angiogenesis and tumor growth: design, synthesis, and optimization of pharmacokinetics and biological activities". Journal of Medicinal Chemistry 48 (8): 2838–46. doi:10.1021/jm0401560. PMID 15828822.
^ Sorbera LA, Bayes M (2005). "ABT-510: oncolytic angiogenesis inhibitor". Drugs of the future (Prous Science) 30 (11): 1081–6. doi:10.1358/dof.2005.030.11.949588.

External links

Thrombospondins at the US National Library of Medicine Medical Subject Headings (MeSH)
THBS1, THBS2, THBS3, THBS4, COMP (also known as "THBS5")

UpToDate Contents

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English Journal

Bioactive nanofibers enable the identification of thrombospondin 2 as a key player in enamel regeneration.

Huang Z1, Newcomb CJ2, Lei Y1, Zhou Y1, Bornstein P3, Amendt BA4, Stupp SI5, Snead ML6.
Biomaterials.Biomaterials.2015 Aug;61:216-28. doi: 10.1016/j.biomaterials.2015.05.035. Epub 2015 May 19.
Tissue regeneration and development involves highly synchronized signals both between cells and with the extracellular environment. Biomaterials can be tuned to mimic specific biological signals and control cell response(s). As a result, these materials can be used as tools to elucidate cell signali
PMID 26004236

Downregulation of A disintegrin and metallopeptidase with thrombospondin motif type 1 by DNA hypermethylation in human gastric cancer.

Chen J1, Zhang C1, Xu X1, Zhu X1, Dai D1.
Molecular medicine reports.Mol Med Rep.2015 Aug;12(2):2487-94. doi: 10.3892/mmr.2015.3667. Epub 2015 Apr 23.
A disintegrin and metallopeptidase with thrombospondin motif type 1 (ADAMTS1) is a metalloproteinase with antiangiogenic activity. It was previously observed that the mRNA and protein levels of ADAMTS1 are downregulated in primary gastric tumors. The aim of the present study was to examine whether
PMID 25936341

Leptin modulates the expression of catabolic genes in rat nucleus pulposus cells through the mitogen‑activated protein kinase and Janus kinase 2/signal transducer and activator of transcription 3 pathways.

Miao D1, Zhang L1.
Molecular medicine reports.Mol Med Rep.2015 Aug;12(2):1761-8. doi: 10.3892/mmr.2015.3646. Epub 2015 Apr 20.
Obesity has been demonstrated to be involved in the progress of intervertebral disc degeneration (IDD). However, the associated mechanisms remain to be elucidated. The purpose the present study was to examine the effect of leptin on the expression of degeneration‑associated genes in rat nucleus pu
PMID 25892402

Japanese Journal

Thrombospondin-1 Is a Putative Target Gene of Runx2 and Runx3

Shi Xiuming,Deepak Vishwa,Wang Linghui,Ba Xueqing,Komori Toshihisa,Zeng Xianlu,Liu Wenguang
International Journal of Molecular Sciences 14(7), 14321-14332, 2013-07-10
… Thrombospondin-1 (TSP-1), a matricellular protein widely acclaimed to be involved in the inhibition of angiogenesis and tumorigenesis, is synthesized and secreted by many cell types, including osteoblast and cancer cells. …
NAID 120005322500

Thrombospondin-1 in Urological Cancer: Pathological Role, Clinical Significance, and Therapeutic Prospects

Miyata Yasuyoshi,Sakai Hideki
International Journal of Molecular Sciences 14(6), 12249-12272, 2013-06-07
Angiogenesis is an important process for tumor growth and progression of various solid tumors including urological cancers. Thrombospondins (TSPs), especially TSP-1, are representative "anti"-angiogen …
NAID 120005306853

Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway in cultured human chondrocytes

Saito T.,Nishida K.,Furumatsu T.,Yoshida A.,Ozawa M.,Ozaki T.
Osteoarthritis and Cartilage 21(1), 165-174, 2013-01-00
… Objective: To investigate the inhibitory effects and the regulatory mechanisms of histone deacetylase (HDAC) inhibitors on mechanical stress-induced gene expression of runt-related transcription factor (RUNX)-2 and a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 in human chondrocytes. …
NAID 120005311990

Related Pictures

★リンクテーブル★

リンク元	「TSP」「トロンボスポンジン」
拡張検索	「thrombospondin 1」

「TSP」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Thrombospondin type 1 domain
	Thrombospondin-1
Identifiers
Symbol	TSP_1
Pfam	PF00090
InterPro	IPR000884
SMART	SM00209
PROSITE	PS50092
SCOP	1lsl
SUPERFAMILY	1lsl
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary