Hurford Jr KR, Cobrinik D, Lee HM, Dyson N.. pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes. Genes Dev 11: 1447-1463

Department of Medicine, Boston University, Boston, Massachusetts, United States
Genes & Development (Impact Factor: 10.8). 07/1997; 11(11):1447-63. DOI: 10.1101/gad.11.11.1447
Source: PubMed


The activity of the E2F transcription factor is controlled by physical association with the retinoblastoma protein (pRB) and two related proteins, p107 and p130. The pRB family members are thought to control different aspects of E2F activity, but it has been unclear what the respective functions of these proteins might be. To dissect the specific functions of pRB, p107, and p130 we have investigated how the expression of E2F-regulated genes is changed in cultures of primary cells lacking each of these family members. Whereas no changes were found in the expression of E2F-target genes in cells lacking either p107 or p130, deregulated expression of E2F targets was seen in cells lacking pRB and in cells lacking both p107 and p130. Surprisingly, the genes that were disregulated in these two settings were completely different. These findings show that pRB and p107/p130 indeed provide different functions in E2F regulation and identify target genes that are dependent on pRB family proteins for their normal expression.

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    • "Importantly, pocket proteins are differentially expressed along the cell cycle, probably reflecting specific functions for each protein during the different cell cycle phases. In general, pRb and p107 are expressed in cycling cells, while p130 is preferentially expressed in quiescent cells, but this aspect is also cell type specific (43, 47, 48). "
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    • "The expression level of p107 is high only in proliferating cells, but knockdown of p130 results in increased expression of p107, which results in the formation of a p107-DREAM complex in quiescent cells. However, p130-/-/p107-/- mouse embryonic fibroblasts lose the ability to form a functional DREAM complex and fail to repress E2F-dependent genes expression during quiescence, causing cells to re-enter the cell cycle [21]. E2F4-/-/E2F5-/- mouse embryonic fibroblasts can also re-enter the cell cycle from quiescence but fail to arrest in the G1 phase when the CDK inhibitor INK4A is overexpressed [22]. "
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    10/2013; 2(1):29. DOI:10.1186/2162-3619-2-29
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    • "Mouse embryonic fibroblasts (MEFs) were generated from E13.5 embryos using standard procedures and cultured in DMEM with 10% FBS and antibiotics [42]. Retroviral transduction with pBABE-HrasV12 was as reported by Serrano et al. [43] and viruses were packaged in Bosc-23 cells. "
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