Tissue inhibitor of metalloproteinase


The matrix metalloproteinases are inhibited by specific endogenous tissue inhibitors of metalloproteinases, which comprise a family of four protease inhibitors: TIMP1, TIMP2, TIMP3 and TIMP4. A member of the TIMP family, TIMP3, has been observed progressively downregulated in Human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. For this reason, TIMP3 is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression.
Overall, all MMPs are inhibited by TIMPs once they are activated but the gelatinases can form complexes with TIMPs when the enzymes are in the latent form.
The complex of latent MMP-2 with TIMP-2 serves to facilitate the activation of pro-MMP-2 at the cell surface by MT1-MMP, a membrane-anchored MMP.
The role of the pro-MMP-9/TIMP-1 complex is still unknown.