A NOVEL MEMBER OF HUMAN TISSUE INHIBITOR OF METALLOPROTEINASES (TIMP) GENE FAMILY IS REGULATED DURING G(1) PROGRESSION, MITOGENIC STIMULATION, DIFFERENTIATION, AND SENESCENCE

作者：WICK M; BURGER C; BRUSSELBACH S; LUCIBELLO FC; MULLER R

来源：Journal of Biological Chemistry, 1994, 269(29): 18953-18960.

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-G(1). 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 G(1). In contrast, mig-5 expression is decreased in senescent human fibroblasts, suggesting that these cells may be blocked at a stage in G(1) 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 G(1), this gene should represent an invaluable tool for the analysis of cell cycle progression, terminal differentiation, and replicative senescence.

• 出版日期1994-7-22