Functional potential of P2P‐R: A role in the cell cycle and cell differentiation related to its interactions with proteins that bind to matrix associated regions of DNA?

P2P‐R is the alternately spliced product of the P2P‐R/PACT gene in that P2P‐R lacks one exon encoding 34 amino acids. The 250 kDa P2P‐R protein is the predominate product expressed in multiple murine cell lines. It is a highly basic protein that contains multiple domains including an N‐terminal RING type zinc finger, a proline rich domain, an RS region, and a C‐terminal lysine‐rich domain. P2P‐R binds the p53 and the Rb1 tumor suppressors and is phosphorylated by the cdc2 and SRPK1a protein kinases. P2P‐R also interacts with scaffold attachment factor‐B (SAF‐B), a well characterized MARs (for matrix attachment regions) binding factor, and may interact with nucleolin, another MARs binding factor. In addition, P2P‐R binds single strand DNA (ssDNA). The expression of P2P‐R is regulated by differentiation and cell cycle events. P2P‐R mRNA is markedly repressed during differentiation, whereas immunoreactive P2P‐R protein levels are >10‐fold higher in mitotic than in G 0 cells. The localization of P2P‐R also is modulated during the cell cycle. During interphase, P2P‐R is present primarily in nucleoli and nuclear speckles whereas during mitosis, P2P‐R associates with the periphery of chromosomes. Overexpression of near full length P2P‐R induces mitotic arrest in prometaphase and mitotic apoptosis, and overexpression of selected P2P‐R segments also can promote apoptosis. This compendium of data supports the possibility that P2P‐R may form complexes with the Rb1 and/or p53 tumor suppressors and MARs‐related factors, in a cell cycle and cell differentiation‐dependent manner, to influence gene transcription/expression and nuclear organization. J. Cell. Biochem. 90: 6–12, 2003. © 2003 Wiley‐Liss, Inc.