TIMP1
TIMP metallopeptidase inhibitor 1,also known asTIMP1,atissue inhibitor of metalloproteinases,is a glycoprotein with a molecular weight of 28 kDa.[5]TIMP1 is expressed from several tissues of organisms.
This protein is a member of theTIMP family.Theglycoproteinis a naturalinhibitorof thematrix metalloproteinases(MMPs), a group of peptidases involved in degradation of theextracellular matrix.In addition to its inhibitory role against most of the known MMPs, the encoded protein is able to promotecellproliferation in a wide range of cell types, and may also have an anti-apoptotic function.
Function
[edit]TIMP1 is an inhibitory molecule that regulates matrix metalloproteinases (MMPs), and disintegrin-metalloproteinases (ADAMs and ADAMTSs).[6]In regulating MMPs, TIMP1 plays a crucial role in extracellular matrix (ECM) composition, wound healing,[7]and pregnancy.[8][9][10]
The dysregulated activity of TIMP1 has been implicated in cancer.[11]In pregnancy, TIMP1 plays a regulatory role in the process of implantation, particularly the cytotrophoblast invasion of the uterine endometrium.[12]Additionally, it plays a role in regulating the transcriptional profile of fetal and placental tissues associated with the early stages of pregnancy.[13]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 manipulatedin vitrousing techniques, like the TIMP1 knock-out.[14][15][16]
Other names
[edit]- Erythroid potentiating activity (EPA)
- Human collagenase inhibitor (HCI)
Regulation of TIMP expression
[edit]Transcriptionof thisgeneis highly inducible in response to manycytokinesandhormones.In addition, the expression from some but not all inactiveX chromosomessuggests that this gene inactivation is polymorphic inhumanfemales.This gene is located within intron 6 of thesynapsin Igene and is transcribed in the opposite direction.[17]
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.[18]
Increased expression of TIMP1 has been found to be associated with worse prognosis of various tumors, such aslaryngeal carcinoma[19]ormelanoma.[20]
See also
[edit]References
[edit]- ^abcGRCh38: Ensembl release 89: ENSG00000102265–Ensembl,May 2017
- ^abcGRCm38: Ensembl release 89: ENSMUSG00000001131–Ensembl,May 2017
- ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^Nee, Larine E.; Mcmorrow, Tara; Campbell, Eric; Slattery, Craig; Ryan, Michael P. (2004-10-01)."TNF-α and IL-1β–mediated regulation of MMP-9 and TIMP-1 in renal proximal tubular cells".Kidney International.66(4): 1376–1386.doi:10.1111/j.1523-1755.2004.00900.x.ISSN0085-2538.PMID15458430.
- ^Brew K, Nagase H (January 2010)."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.doi:10.1016/j.bbamcr.2010.01.003.PMC2853873.PMID20080133.
- ^Brew K, Dinakarpandian D, Nagase H (March 2000). "Tissue inhibitors of metalloproteinases: evolution, structure and function".Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology.1477(1–2): 267–83.doi:10.1016/S0167-4838(99)00279-4.PMID10708863.
- ^Graham CH, Lala PK (August 1991). "Mechanism of control of trophoblast invasion in situ".Journal of Cellular Physiology.148(2): 228–34.doi:10.1002/jcp.1041480207.PMID1652588.S2CID3145982.
- ^Nothnick WB, Soloway P, Curry TE (May 1997)."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): 1181–8.doi:10.1095/biolreprod56.5.1181.PMID9160717.
- ^Nothnick WB (September 2000)."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): 905–12.doi:10.1095/biolreprod63.3.905.PMID10952938.
- ^Kim YS, Kim SH, Kang JG, Ko JH (2012)."Expression level and glycan dynamics determine the net effects of TIMP-1 on cancer progression".BMB Reports.45(11): 623–8.doi:10.5483/BMBRep.2012.45.11.233.PMC4133808.PMID23187000.
- ^Graham CH, Lala PK (August 1991). "Mechanism of control of trophoblast invasion in situ".Journal of Cellular Physiology.148(2): 228–34.doi:10.1002/jcp.1041480207.PMID1652588.S2CID3145982.
- ^Vincent ZL, Mitchell MD, Ponnampalam AP (December 2015)."Regulation of TIMP-1 in Human Placenta and Fetal Membranes by lipopolysaccharide and demethylating agent 5-aza-2'-deoxycytidine".Reproductive Biology and Endocrinology.13:136.doi:10.1186/s12958-015-0132-y.PMC4687108.PMID26691525.
- ^Gong Y, Scott E, Lu R, Xu Y, Oh WK, Yu Q (2013-10-15)."TIMP-1 promotes accumulation of cancer associated fibroblasts and cancer progression".PLOS ONE.8(10): e77366.Bibcode:2013PLoSO...877366G.doi:10.1371/journal.pone.0077366.PMC3797040.PMID24143225.
- ^Jourquin J, Tremblay E, Bernard A, Charton G, Chaillan FA, Marchetti E, Roman FS, Soloway PD, Dive V, Yiotakis A, Khrestchatisky M, Rivera S (November 2005). "Tissue inhibitor of metalloproteinases-1 (TIMP-1) modulates neuronal death, axonal plasticity, and learning and memory".The European Journal of Neuroscience.22(10): 2569–78.doi:10.1111/j.1460-9568.2005.04426.x.PMID16307599.S2CID18499513.
- ^Graham CH, Lala PK (August 1991). "Mechanism of control of trophoblast invasion in situ".Journal of Cellular Physiology.148(2): 228–34.doi:10.1002/jcp.1041480207.PMID1652588.S2CID3145982.
- ^"Entrez Gene: TIMP1 TIMP metallopeptidase inhibitor 1".
- ^Reichenstein M, Reich R, LeHoux JG, Hanukoglu I (February 2004). "ACTH induces TIMP-1 expression and inhibits collagenase in adrenal cortex cells".Molecular and Cellular Endocrinology.215(1–2): 109–14.CiteSeerX10.1.1.538.7614.doi:10.1016/j.mce.2003.11.011.PMID15026182.S2CID6836003.
- ^Ma J, Wang J, Fan W, Pu X, Zhang D, Fan C, Xiong L, Zhu H, Xu N, Chen R, Liu S (Dec 2013)."Upregulated TIMP-1 correlates with poor prognosis of laryngeal squamous cell carcinoma".International Journal of Clinical and Experimental Pathology.7(1): 246–54.PMC3885479.PMID24427345.
- ^Tarhini AA, Lin Y, Yeku O, LaFramboise WA, Ashraf M, Sander C, Lee S, Kirkwood JM (January 2014)."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.doi:10.1186/1479-5876-12-19.PMC3909384.PMID24457057.
Further reading
[edit]- Hornebeck W (December 2003). "Down-regulation of tissue inhibitor of matrix metalloprotease-1 (TIMP-1) in aged human skin contributes to matrix degradation and impaired cell growth and survival".Pathologie-Biologie.51(10): 569–73.doi:10.1016/j.patbio.2003.09.003.PMID14622947.
- Gardner J, Ghorpade A (December 2003)."Tissue inhibitor of metalloproteinase (TIMP)-1: the TIMPed balance of matrix metalloproteinases in the central nervous system".Journal of Neuroscience Research.74(6): 801–6.doi:10.1002/jnr.10835.PMC3857704.PMID14648584.
External links
[edit]- TheMEROPSonline database for peptidases and their inhibitors:I35.001
- Overview of all the structural information available in thePDBforUniProt:P01033(Metalloproteinase inhibitor 1) at thePDBe-KB.