REGULATION OF P130 DURING THE CELL CYCLE AND QUIESCENCE

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DESCRIPTION: p130 is a member of the retinoblastoma family of pocket proteins, which so far is represented by two other proteins, the retinoblastoma tumor suppressor protein (pRb) and p107. This family of proteins shares the ability to suppress growth in a variety of cell types and its members are believed to play a pivotal role in cell cycle control and differentiation. In addition, pRb has been implicated in the genesis of several types of cancer suggesting that its related counterparts, p107 and p130, may also be implicated. Indeed, the p130 gene maps to a region of chromosome 16 found deleted in a set of human tumors. Although pRb is one of the best characterized tumor suppressor proteins, very little is known about p107 and p130. Our results suggest that p130 is regulated during the cell cycle. In particular, we have observed major changes in the phosphorylation status of p130 at the G0/G1 transition and in mid-to-late G1. The experiments proposed in this application are aimed at understanding the mechanisms and proteins involved in the regulation of p130 at the G0/G1 transition and during the cell cycle. The aims of this proposal are: 1, to establish whether cyclin/CDK holoenzymes are involved in the phosphorylation of p130 during the cell cycle. 2, to characterize the protein phosphatase(s) involved in the dephosphorylation of p130. 3, to ascertain whether phosphorylation of p130 during the cell cycle regulates its association with other cellular proteins. 4, to determine the existence of functional relationships between pocket proteins, in particular between pRb and p130. Once we meet these aims, we will gain insights into our understanding of the regulation of the G0/G1 transition and the commitment to the cell cycle.