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- W1568168120 abstract "Proc Amer Assoc Cancer Res, Volume 47, 20061542 We recently identified the PD2 gene, co-localized on the 19q13 amplicon with AKT2. This gene presents transforming activity when overexpressed in fibroblast cells. The PD2 gene encodes the human RNA polymerase II factor 1 (hPAF1), a member of the PAF1 complex. The PAF1 complex is part of the RNA polymerase II transcription apparatus and regulates multiple steps in gene expression. The PAF1 complex acts as a docking protein in between the complexes Rad6-Bre1, COMPASS-Dot1p, and the phosphorylated carboxyl terminal domain of the RNA polymerase II. As such, PAF1 is directly involved in transcription elongation via histone H2B ubiquitination and histone H3 methylation. Herein, we report that hPAF1 presents a cyclin-like oscillatory expression pattern during the cell-cycle progression. hPAF1 is first detected in the early G1 phase, increases during the S phase, and reaches a maximum level of expression in the G2 phase. Synthesized as a 60 kDa protein, hPAF1 translocates as an 80 kDa protein to the nucleus. In prophase, hPAF1 aligns in filament-like structures, migrates at the pole in metaphase to form a crown surrounding the centrosomes, and is degraded during the metaphase to anaphase transition. We show that hPAF1 delays S-phase entry but favor the G2/M transition. More specifically, hPAF1 positively regulates the transcription of cyclin B1 and Cdk1 and also regulates cyclins A1, A2, D1, and E1. hPAF1 also interacts with both phosphorylated forms of the DNA polymerase α-primase complex, that mediate the replication initiation and elongation mechanisms. Because hPAF1 delays S-phase entry, we hypothesized that hPAF1/DNA polymerase α-primase interaction might limit the DNA polymerase α-primase activity during the replication process. Altogether, hPAF1 and the PAF1 complex appear as potent regulators of the cell-cycle progression, acting as a tumor suppressor. Dysregulation of at least one of the PAF1 members via gene amplification or overexpression leads to the transforming phenotype." @default.
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- W1568168120 date "2006-04-15" @default.
- W1568168120 modified "2023-09-28" @default.
- W1568168120 title "Early G1-phase inhibition of cell cycle progression by Wee1 inhibitor PD0166285 in the B16 mouse melanoma cell line" @default.
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