IPP5, a novel inhibitor of protein phosphatase 1, suppresses tumor growth and progression of cervical carcinoma cells by inducing G2/M arrest.

Protein phosphatase 1 (PP1) is a major serine/threonine phosphatase that controls gene expression and cell cycle progression. Here, we report the characterization of a novel human bone marrow stromal cell (BMSC)-derived protein called protein phosphatase 1 inhibitor 5 (IPP5), which was obtained by large-scale random sequencing of a human BMSC cDNA library. The human IPP5 cDNA encodes a protein of 116 amino acid residues, which shares high homology with human protein phosphatase 1 inhibitor-1 (PPI-1). The effect of IPP5 on tumor growth and the underlying molecular mechanisms were investigated by overexpression of IPP5 in HeLa cells, a human cervical carcinoma cell line. Our results demonstrated that overexpression of the active mutant IPP5 inhibited the growth of HeLa cells both in vitro and in vivo. Biochemical analysis demonstrated that active mutant IPP5-mediated G2/M arrest of HeLa cells involved regulation of cyclin A1, cyclin B1, CDK1, p21, and p53, as well as increased inhibition of ERK activation. Furthermore, overexpression of the active mutant IPP5 leads to the formation of dikaryons following the failure of cytokinesis. Therefore, IPP5 might be a potential growth inhibitor for human tumor cells, especially for cervical carcinoma cells, and it could contribute to the development of new therapeutic strategies for human cervical cancer treatment.