The role of Krs1 in cell cycle arrest.
The Krs1 (kinase responsive to stress 1) kinase has been proposed to mediate signals initiated by various forms of cellular or environmental stress for the process of growth arrest and apoptosis. The functional role of Krs1 in cell growth arrest may involve a constant, stress-independent proteolytic modification of the full-length kinase p63(Krs1), via caspase-like activity, to produce kinase-active kinase fragment, p33(Krs1). Induction of the kinase activity of p33(Krs1) is closely correlated with cell growth arrest in the G(0)/G(1) phase due to serum starvation, contact inhibition or growth-arresting agents. Deactivation of p33(Krs1) is closely associated with cell entry into the cell cycle. In response to stress shock the conversion of p63(Krs1) to p33(Krs1) is enhanced, and the kinase activity of p33(Krs1) is additionally increased in quiescent cells that undergo apoptosis. Both mechanisms of proteolytic modification and protein phosphorylation are involved in a complex control of the kinase activity and function of p33(Krs1) in response to environmental changes leading to cell growth arrest in quiescence or quiescence-related apoptosis. Numerous studies have shown that signaling pathways in malignantly transformed cells are regulated differently from their counterpart pathways in normal counterpart cells in response to stress shock or anticancer agents. It is desirable to develop one type of anticancer agent to selectively growth-arrest normal counterpart cells in G(0)/G(1) phase of the cell cycle through the control of Krs1-involved signaling pathways. The success of arresting normal cells in a quiescent state will provide access for other types of anticancer treatments to induce cell death of cancerous cells, which are resistant to growth arrest in other phases of the cell cycle.
Wang
Hwa-Chain Robert
HC
Department of Pathobiology, College of Veterinary Medicine, The University of Tennessee, Knoxville, Tennessee, USA. hcrwang@utk.edu
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D000090742:Serine-Threonine Kinase 3; D015398:Signal Transduction; D000099317:Hippo Kinases
D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; C097835:STK3 protein, human; D000099317:Hippo Kinases