The role of the PPM1D gene in tumor pathogenesis.

Abstract

The PPM1D gene and its protein product (serine-threonine protein phosphatase, PPM1D or Wip1) are involved in regulation of cell's DNA damage response, cell cycle control, and repair. Amplification, overexpression, or mutations of the PPM1D gene have a significant impact on cell responses to stress factors and genetic instability as well as impairments of processes of double-strand break repair, nucleotide excision repair, base excision repair, cell cycle, and apoptosis. PPM1D dephosphorylates and thus inactivates p53, proteins that respond to DNA strand integrity damage, cell cycle checkpoint proteins, and apoptotic proteins. This contributes to tumor development, growth, and maintenance of the tumor phenotype. In this review we consider data on the role of the PPM1D gene in the formation and maintenance of various oncological processes, including tumors of the mammary glands, ovaries, prostate gland, esophagus, stomach, intestines, liver and pancreas, hemoblastoses, and others.