Biology:TIMP1

From HandWiki

TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a two-domain glycoprotein with a molecular weight of 28 kDa.[1] TIMP1 is expressed in several tissues of organisms.

This protein is a member of the TIMP family. The glycoprotein is a natural inhibitor of the matrix metalloproteinases (MMPs), a group of peptidases involved in degradation of the extracellular matrix. In addition to its inhibitory role against most of the known MMPs, the encoded protein is able to promote cell proliferation in a wide range of cell types, and may also have an anti-apoptotic function.

Function

TIMP1 is an inhibitory molecule that regulates matrix metalloproteinases (MMPs) and disintegrin-metalloproteinases (ADAMs and ADAMTSs) through binding of the TIMP1 N-terminal domain to the metalloproteinase active site.[2] It has also been suggested that the C-terminal domain of TIMP1 can bind to the inactive precursors pro-MMP-2 and pro-MMP-9.[3] In regulating MMPs, TIMP1 plays a crucial role in extracellular matrix (ECM) composition, wound healing,[4] and pregnancy.[5][6][7]

The dysregulated activity of TIMP1 has been implicated in inflammation, cancer, and fibrosis.[8][9][10] In pregnancy, TIMP1 plays a regulatory role in the process of implantation, particularly the cytotrophoblast invasion of the uterine endometrium.[11] Additionally, it plays a role in regulating the transcriptional profile of fetal and placental tissues associated with the early stages of pregnancy.[12] Studies attribute this role to a mechanism involving the chromatin structure at the TIMP1 promoter region, implicating new pharmaceutical possibilities for the therapeutic regulation of TIMP1. Accordingly, TIMP1 can be manipulated in vitro using techniques, like the TIMP1 knock-out.[13][14][15]

Cell-surface receptor binding

While traditionally reported for its protease-inhibiting ability, the C-terminal domain of TIMP1 has been shown to bind to cell-surface receptors including the tetraspanins CD63 and CD82.[16] These interactions can activate downstream signaling pathways including the MAPK pathway.[17]

Other names

  • Erythroid potentiating activity (EPA)
  • Human collagenase inhibitor (HCI)

Regulation of TIMP expression

Transcription of this gene is highly inducible in response to many cytokines and hormones. In addition, the expression from some but not all inactive X chromosomes suggests that this gene inactivation is polymorphic in human females. This gene is located within intron 6 of the synapsin I gene and is transcribed in the opposite direction.[18]

In adrenocortical cells the trophic hormone ACTH induces expression of TIMP-1 and the increase in TIMP expression is also associated with decreased collagenase activity.[19]

Increased expression of TIMP1 has been found to be associated with worse prognosis of various tumors, such as laryngeal carcinoma[20] or melanoma.[21]

See also

References

  1. ↑ "TNF-α and IL-1β–mediated regulation of MMP-9 and TIMP-1 in renal proximal tubular cells". Kidney International 66 (4): 1376–1386. 2004-10-01. doi:10.1111/j.1523-1755.2004.00900.x. ISSN 0085-2538. PMID 15458430. 
  2. ↑ "The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1803 (1): 55–71. January 2010. doi:10.1016/j.bbamcr.2010.01.003. PMID 20080133. 
  3. ↑ "Kinetic Analysis of the Binding of Human Matrix Metalloproteinase-2 and -9 to Tissue Inhibitor of Metalloproteinase (TIMP)-1 and TIMP-2*". The Journal of Biological Chemistry 272 (47): 29975–29983. 1997-11-21. doi:10.1074/jbc.272.47.29975. ISSN 0021-9258. PMID 9368077. 
  4. ↑ "Tissue inhibitors of metalloproteinases: evolution, structure and function". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology 1477 (1–2): 267–283. March 2000. doi:10.1016/S0167-4838(99)00279-4. PMID 10708863. 
  5. ↑ "Mechanism of control of trophoblast invasion in situ". Journal of Cellular Physiology 148 (2): 228–234. August 1991. doi:10.1002/jcp.1041480207. PMID 1652588. 
  6. ↑ "Assessment of the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) during the periovulatory period in female mice lacking a functional TIMP-1 gene". Biology of Reproduction 56 (5): 1181–1188. May 1997. doi:10.1095/biolreprod56.5.1181. PMID 9160717. 
  7. ↑ "Disruption of the tissue inhibitor of metalloproteinase-1 gene results in altered reproductive cyclicity and uterine morphology in reproductive-age female mice". Biology of Reproduction 63 (3): 905–912. September 2000. doi:10.1095/biolreprod63.3.905. PMID 10952938. 
  8. ↑ "Cut loose TIMP-1: an emerging cytokine in inflammation". Trends in Cell Biology 33 (5): 413–426. May 2023. doi:10.1016/j.tcb.2022.08.005. ISSN 0962-8924. PMID 36163148. 
  9. ↑ "Tissue Inhibitor of Matrix Metalloproteinase-1 Promotes Myocardial Fibrosis by Mediating CD63–Integrin β1 Interaction". Hypertension (Dallas, Tex.) 69 (6): 1092–1103. June 2017. doi:10.1161/HYPERTENSIONAHA.117.09045. PMID 28373589. https://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.117.09045. 
  10. ↑ "Expression level and glycan dynamics determine the net effects of TIMP-1 on cancer progression". BMB Reports 45 (11): 623–628. Nov 2012. doi:10.5483/BMBRep.2012.45.11.233. PMID 23187000. 
  11. ↑ "Mechanism of control of trophoblast invasion in situ". Journal of Cellular Physiology 148 (2): 228–234. August 1991. doi:10.1002/jcp.1041480207. PMID 1652588. 
  12. ↑ "Regulation of TIMP-1 in Human Placenta and Fetal Membranes by lipopolysaccharide and demethylating agent 5-aza-2'-deoxycytidine". Reproductive Biology and Endocrinology 13. December 2015. doi:10.1186/s12958-015-0132-y. PMID 26691525. 
  13. ↑ "TIMP-1 promotes accumulation of cancer associated fibroblasts and cancer progression". PLOS ONE 8 (10). 2013-10-15. doi:10.1371/journal.pone.0077366. PMID 24143225. Bibcode: 2013PLoSO...877366G. 
  14. ↑ "Tissue inhibitor of metalloproteinases-1 (TIMP-1) modulates neuronal death, axonal plasticity, and learning and memory". The European Journal of Neuroscience 22 (10): 2569–2578. November 2005. doi:10.1111/j.1460-9568.2005.04426.x. PMID 16307599. 
  15. ↑ "Mechanism of control of trophoblast invasion in situ". Journal of Cellular Physiology 148 (2): 228–234. August 1991. doi:10.1002/jcp.1041480207. PMID 1652588. 
  16. ↑ "Identification of CD63 as a tissue inhibitor of metalloproteinase-1 interacting cell surface protein". The EMBO Journal 25 (17): 3934–3942. 2006-08-17. doi:10.1038/sj.emboj.7601281. ISSN 0261-4189. PMID 16917503. 
  17. ↑ "Novel functions of TIMPs in cell signaling". Cancer and Metastasis Reviews 25 (1): 99–113. March 2006. doi:10.1007/s10555-006-7893-x. ISSN 0167-7659. PMID 16680576. 
  18. ↑ "Entrez Gene: TIMP1 TIMP metallopeptidase inhibitor 1". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=7076. 
  19. ↑ "ACTH induces TIMP-1 expression and inhibits collagenase in adrenal cortex cells". Molecular and Cellular Endocrinology 215 (1–2): 109–114. February 2004. doi:10.1016/j.mce.2003.11.011. PMID 15026182. 
  20. ↑ "Upregulated TIMP-1 correlates with poor prognosis of laryngeal squamous cell carcinoma". International Journal of Clinical and Experimental Pathology 7 (1): 246–254. Dec 2013. PMID 24427345. 
  21. ↑ "A four-marker signature of TNF-RII, TGF-α, TIMP-1 and CRP is prognostic of worse survival in high-risk surgically resected melanoma". Journal of Translational Medicine 12: 19. January 2014. doi:10.1186/1479-5876-12-19. PMID 24457057. 

Further reading

  • The MEROPS online database for peptidases and their inhibitors: I35.001
  • Overview of all the structural information available in the PDB for UniProt: P01033 (Metalloproteinase inhibitor 1) at the PDBe-KB.



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:TIMP1&oldid=4474779"