関: TTP

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/01 10:32:23」(JST)

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Tristetraprolin (TTP), also known as zinc finger protein 36 homolog (ZFP36), is a protein that in humans, mice and rats is encoded by the ZFP36 gene.^[1]^[2] It is a member of the TIS11 (TPA-induced sequence) family, along with butyrate response factors 1 and 2.^[3]

TTP binds to AU-rich elements (AREs) in the 3'-untranslated regions (UTRs) of the mRNAs of some cytokines and promotes their degradation. For example, TTP is a component of a negative feedback loop that interferes with TNF-alpha production by destabilizing its mRNA.^[4] Mice deficient in TTP develop a complex syndrome of inflammatory diseases.^[4]

Interactions

ZFP36 has been shown to interact with 14-3-3 protein family members, such as YWHAH,^[5] and with NUP214, a member of the nuclear pore complex.^[6]

Regulation

Post-transcriptionally, TTP is regulated in several ways.^[3] The subcellular localization of TTP is influenced by interactions with protein partners such as the 14-3-3 family of proteins. These interactions and, possibly, interactions with target mRNAs are affected by the phosphorylation state of TTP, as the protein can be posttranslationally modified by a large number of protein kinases.^[3] There is some evidence that the TTP transcript may also be targeted by microRNAs, such as miR-29a.^[3]

References

^ DuBois RN, McLane MW, Ryder K, Lau LF, Nathans D (Dec 1990). "A growth factor-inducible nuclear protein with a novel cysteine/histidine repetitive sequence". J Biol Chem 265 (31): 19185–91. PMID 1699942.
^ "Entrez Gene: ZFP36 zinc finger protein 36, C3H type, homolog (mouse)".
^ ^a ^b ^c ^d Sanduja S, Blanco FF, Dixon DA (2011). "The roles of TTP and BRF proteins in regulated mRNA decay". Wiley Interdiscip Rev RNA 2 (1): 42–57. doi:10.1002/wrna.28. PMC 3030256. PMID 21278925.
^ ^a ^b Carballo E, Lai WS, Blackshear PJ (August 1998). "Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin". Science 281 (5379): 1001–5. doi:10.1126/science.281.5379.1001. PMID 9703499.
^ Johnson BA, Stehn JR, Yaffe MB, Blackwell TK (May 2002). "Cytoplasmic localization of tristetraprolin involves 14-3-3-dependent and -independent mechanisms". J. Biol. Chem. 277 (20): 18029–36. doi:10.1074/jbc.M110465200. PMID 11886850.
^ Carman JA, Nadler SG (March 2004). "Direct association of tristetraprolin with the nucleoporin CAN/Nup214". Biochem. Biophys. Res. Commun. 315 (2): 445–9. doi:10.1016/j.bbrc.2004.01.080. PMID 14766228.

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1. 喘息における吸入ステロイドの分子学的影響 molecular effects of inhaled glucocorticoid therapy in asthma

English Journal

Tristetraprolin Limits Inflammatory Cytokine Production in Tumor-Associated Macrophages in an mRNA Decay-Independent Manner.

Kratochvill F1, Gratz N2, Qualls JE1, Van De Velde LA1, Chi H3, Kovarik P4, Murray PJ5.
Cancer research.Cancer Res.2015 Aug 1;75(15):3054-64. doi: 10.1158/0008-5472.CAN-15-0205. Epub 2015 Jul 16.
Tristetraprolin (TTP) is an inducible zinc finger AU-rich RNA-binding protein essential for enforcing degradation of mRNAs encoding inflammatory chemokines and cytokines. Most studies on TTP center on the connection between mRNA half-life and inflammatory output, because loss of TTP amplifies inflam
PMID 26183929

Pro-inflammatory cytokines reduce human TAFI expression via tristetraprolin-mediated mRNA destabilisation and decreased binding of HuR.

Komnenov D, Scipione CA, Bazzi ZA, Garabon JJ, Koschinsky ML, Boffa MB1.
Thrombosis and haemostasis.Thromb Haemost.2015 Jul 28;114(2):337-49. doi: 10.1160/TH14-08-0653. Epub 2015 Jun 11.
Thrombin activatable fibrinolysis inhibitor (TAFI) is the zymogen form of a basic carboxypeptidase (TAFIa) with both anti-fibrinolytic and anti-inflammatory properties. The role of TAFI in inflammatory disease is multifaceted and involves modulation both of specific inflammatory mediators as well as
PMID 26062599

RNA binding proteins as regulators of immune cell biology.

Newman R1,2, Institute B1,2.
Clinical and experimental immunology.Clin Exp Immunol.2015 Jul 21. doi: 10.1111/cei.12684. [Epub ahead of print]
Sequence-specific RNA binding proteins (RBP) are important regulators of the immune response. RBP modulate gene expression by regulating splicing, polyadenylation, localisation, translation and decay of target mRNAs. Increasing evidence suggests that RBP play critical roles in the development, activ
PMID 26201441

Japanese Journal

TGF-β Decreases the Stability of IL-18-Induced IFN-γ mRNA through the Expression of TGF-β-Induced Tristetraprolin in KG-1 Cells

Inoue Yasumichi,Abe Kenji,Onozaki Kikuo [他],Hayashi Hidetoshi
Biological and Pharmaceutical Bulletin 38(4), 536-544, 2015
… Tristetraprolin (TTP), one of the ARE-binding proteins, destabilizes IFN-γ mRNA, and IL-18 repressed the expression of TTP mRNA. …
NAID 130005062261

炎症制御におけるRNA分解酵素Regnase-1の役割

竹内理
日本薬理学雑誌 145(3), 129-133, 2015
… トカインをはじめとした炎症関連遺伝子発現は，転写調節のみではなく，転写後のmRNA分解速度や翻訳などによって緻密に制御され，適切な炎症応答を保っている．microRNAだけではなく，mRNA不安定化を促すTristetraprolinやRNA分解酵素であるRegnase-1といったmRNAの3′UTRに結合するRNA結合タンパク質が炎症制御に重要であることが明らかになってきた．シグナル伝達経路によりRegnase-1の発現が直接制御されることから，mRNA安定 …
NAID 130004827731

mRNAの安定性制御を介した免疫応答の調節 (第5土曜特集サイトカインと疾患--あらたな病態モデルから治療へ) -- (サイトカインの分泌刺激および産生調節機構)

松下一史,審良静男
医学のあゆみ 234(5), 345-351, 2010-07-31
NAID 40017207572

★リンクテーブル★

リンク元	「トリステトラプロリン」

「トリステトラプロリン」

ZFP36 ring finger protein
	PDB rendering based on 1m9o.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	4J8S
Identifiers
Symbols	ZFP36 ; G0S24; GOS24; NUP475; RNF162A; TIS11; TTP; zfp-36
External IDs	OMIM: 190700 MGI: 99180 HomoloGene: 2558 GeneCards: ZFP36 Gene
Gene ontology
Molecular function	• DNA binding; • single-stranded RNA binding; • mRNA binding; • protein binding; • AU-rich element binding; • protein kinase binding; • C-C chemokine binding; • poly(A) RNA binding; • metal ion binding; • 14-3-3 protein binding;
Cellular component	• nucleus; • cytoplasm; • cytosol; • cytoplasmic stress granule;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; • mRNA catabolic process; • gene expression; • RNA metabolic process; • mRNA metabolic process; • regulation of tumor necrosis factor production; • negative regulation of translation involved in gene silencing by miRNA; • response to starvation; • positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; • 3'-UTR-mediated mRNA stabilization; • positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

　　[★]

英: tristetraprolin、TTP
関: 腫瘍増殖停止時間、血栓性血小板減少性紫斑病、チミジン三リン酸

[pmid1699942-1] DuBois RN, McLane MW, Ryder K, Lau LF, Nathans D (Dec 1990). "A growth factor-inducible nuclear protein with a novel cysteine/histidine repetitive sequence". J Biol Chem 265 (31): 19185–91. PMID 1699942.

[entrez-2] "Entrez Gene: ZFP36 zinc finger protein 36, C3H type, homolog (mouse)".

[pmid21278925-3] Sanduja S, Blanco FF, Dixon DA (2011). "The roles of TTP and BRF proteins in regulated mRNA decay". Wiley Interdiscip Rev RNA 2 (1): 42–57. doi:10.1002/wrna.28. PMC 3030256. PMID 21278925.

[pmid9703499-4] Carballo E, Lai WS, Blackshear PJ (August 1998). "Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin". Science 281 (5379): 1001–5. doi:10.1126/science.281.5379.1001. PMID 9703499.

[pmid11886850-5] Johnson BA, Stehn JR, Yaffe MB, Blackwell TK (May 2002). "Cytoplasmic localization of tristetraprolin involves 14-3-3-dependent and -independent mechanisms". J. Biol. Chem. 277 (20): 18029–36. doi:10.1074/jbc.M110465200. PMID 11886850.

[pmid14766228-6] Carman JA, Nadler SG (March 2004). "Direct association of tristetraprolin with the nucleoporin CAN/Nup214". Biochem. Biophys. Res. Commun. 315 (2): 445–9. doi:10.1016/j.bbrc.2004.01.080. PMID 14766228.

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tristetraprolin