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.
Scott
Robert E
RE
Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. rescott@utmem.edu
Giannakouros
Thomas
T
Gao
Sizhi
S
Peidis
Philippos
P
D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; C104647:PRKRA protein, human; D016601:RNA-Binding Proteins; D004247:DNA