Tissue inhibitor of metalloproteinase

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Tissue inhibitors of metalloproteinases (TIMPs) are specific endogenous protease inhibitors to the matrix metalloproteinases. There are four TIMPs; TIMP1 , TIMP2 , TIMP3 and TIMP4 . [1] TIMP3 has been observed progressively downregulated in Human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. [2] For this reason, TIMP3 is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression. [2]

Overall, all MMPs are inhibited by TIMPs once they are activated but the gelatinases (MMP-2 and MMP-9) can form complexes with TIMPs when the enzymes are in the latent form.

The complex of latent MMP-2 (pro-MMP-2)with TIMP-2 serves to facilitate the activation of pro-MMP-2 at the cell surface by MT1-MMP (MMP-14), a membrane-anchored MMP.

The role of the pro-MMP-9/TIMP-1 complex is still unknown.

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  1. Brew K, Dinakarpandian D, Nagase H (2000). "Tissue inhibitors of metalloproteinases: evolution, structure and function". Biochim Biophys Acta. 1477 (1–2): 267–83. doi:10.1016/S0167-4838(99)00279-4. PMID   10708863.
  2. 1 2 Rotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, Magri E, Selvatici R, Torresani S, Marci R, Garutti P, Negrini M, Tognon M, Martini F (April 2015). "Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes". J Cell Physiol. 230 (4): 802–812. doi:10.1002/jcp.24808. hdl: 11392/2066612 . PMID   25205602.