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Publication : A novel member of human tissue inhibitor of metalloproteinases (TIMP) gene family is regulated during G1 progression, mitogenic stimulation, differentiation, and senescence.

First Author  Wick M Year  1994
Journal  J Biol Chem Volume  269
Issue  29 Pages  18953-60
PubMed ID  8034652 Mgi Jnum  J:19304
Mgi Id  MGI:67481 Doi  10.1016/s0021-9258(17)32259-7
Citation  Wick M, et al. (1994) A novel member of human tissue inhibitor of metalloproteinases (TIMP) gene family is regulated during G1 progression, mitogenic stimulation, differentiation, and senescence. J Biol Chem 269(29):18953-60
abstractText  We have identified in the human diploid fibroblast cell line WI-38 a novel serum-inducible gene, mitogen-inducible gene 5 (mig-5), of the delayed-early class, which represents a new member of the family of human tissue inhibitors of metalloproteinases (TIMPs). The deduced Mig-5 protein shares the highest degree of homology with chicken TIMP-3 (74% identity) and is more distantly related to human TIMP-1 and TIMP-2 (30-38% identity), indicating that mig-5 may represent the human homolog of chicken TIMP-3. In contrast to TIMP-1 and TIMP-2, mig-5 mRNA expression is not only induced in response to mitogenic stimulation but also is subject to cell cycle regulation in normally proliferating WI-38 fibroblasts and HL-60 myeloid cells, showing a clear peak around mid-G1. In agreement with this observation, differentiation of HL-60 cells to either granulocytic or macrophage-like cells leads to increased levels of mig-5 mRNA concomitant with a block in G1. In contrast, mig-5 expression is decreased in senescent human fibroblasts, suggesting that these cells may be blocked at a stage in G1 before or after the phase of maximum mig-5 expression. Since in contrast to the vast majority of other known mitogen-inducible genes, mig-5 expression is periodically up-regulated in G1, this gene should represent an invaluable tool for the analysis of cell cycle progression, terminal differentiation, and replicative senescence.
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