THE P130 POCKET PROTEIN: KEEPING ORDER AT CELL CYCLE EXIT/RE-ENTRANCE TRANSITIONS

Xavier Mayol and Xavier Grana

Fels Institute for Cancer Research and Molecular Biology and Department of Biochemistry and Temple University School of Medicine. 3307 North Broad St., Philadelphia, PA19140

Received 12/5/97 Accepted 12/9/97

4. PERSPECTIVES

The coordinate function of pocket proteins during processes of cell growth and differentiation also implies that biochemical differences must exist between individual pocket protein/E2F complexes. The effects of p130-mediated repression on transcription of certain E2F-responsive genes constitutes one of the first few pieces of evidence in this regard. Thus, p130 function appears to be in charge of repressing the transcription of some genes that should not be expressed or that are not required in situations of cell cycle exit or re-entrance transitions. Our hypothesis is that repression of this genetic program is required for an ordered passage through the regulatory pathways that co-exist in the G1 phase of the cell cycle, including the restriction point transition. Particularly, the order of events that take place to build the restriction point machinery (partially shown in figure 3) suggests that p130: i) participates in keeping this restriction point machinery silent, at least partially, during G0 and early G1; and, ii) participates in the initiation of this process by releasing a pool of free E2F transcription factor, as well as relieving transcriptional repression of some G0-silenced genes. Moreover, additional regulatory pathways involving pocket proteins and other transcriptional regulators in addition to E2F family members should provide more clues about pocket protein function, and this is specially true regarding the biochemical role of p130 during cell cycle exit and differentiation processes. In this respect, identification of the biochemical factors that regulate p130 during cell cycle exit, for instance the hypothetical cell cycle exit-induced kinase activity and differentiation-specific transcription factors putatively targeted by p130, should provide crucial details about the function of p130 during these processes. Therefore, future prospects in the study of p130 function should include the precise dissection of the gene expression programs controlled by p130 and the identification of additional factors that participate in this control.