Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation

Chen, Phang-Lang; Scully, Peter; Shew, Jin‐Yuh; Wang, Jean Y. J.; Lee, Wen‐Hwa

doi:10.1016/0092-8674(89)90517-5

Cited by 915 publications

(539 citation statements)

References 26 publications

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“…cyclin D (Sherr, 1994) and the cyclins responsible for DNA replication and mitosis (cyclins E, A and B). Thus, in contrast to other cell types like ®broblats, where pRb phosphorylation occurs throughout the cell cycle (Buchkovich et al, 1989;Chen et al, 1989;DeCaprio et al, 1989DeCaprio et al, , 1992Mihara et al, 1989) it appears that in 7TD1 cells pRb is phosphorylated predominantly by cyclin D2/CDK4. Indeed, 4 h after the addition of fresh medium, pRb became phosphorylated ( Figure 2b) concomitantly with the increase of cyclin D2 levels (Figure 3b) and the augmentation of cyclin D2/CDK4-associated kinase activity (Figure 3a).…”

Section: Dmso Abrogated Cyclin D2/cdk4 Activity and Impaired Prb Phosmentioning

confidence: 79%

Early G1 growth arrest of hybridoma B cells by DMSO involves cyclin D2 inhibition and p21[CIP1] induction

et al. 1998

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Dimethylsulfoxide (DMSO) was shown to inhibit the proliferation of several B cell lines including Raji, Daudi, and SKW6-CL4 but the mechanisms involved in this growth arrest are still unclear. We show that in 7TD1 mouse hybridoma cells a DMSO-induced reversible G 1 arrest involves inactivation of Rb kinases, cyclin D2/ CDK4 and cyclin E/CDK2. This occurs by at least three distinct mechanisms. Inhibition of cyclin D2 neosynthesis leads to a dramatic decrease of cyclinD2/CDK4 complexes. This in turn enables the redistribution of p27 [KIP1] from cyclin D2/CDK4 to cyclin E/CDK2 complexes. In addition, the simultaneous accumulation of p21 [CIP1] entails increasing association with cyclin D3/ CDK4 and cyclin E/CDK2. Thus, p21 [CIP1] and p27 [KIP1] , act in concert to inhibit cyclin E/CDK2 activity which, together with CDK4 inactivation, confers a G 1 -phase arrest.

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Section: Dmso Abrogated Cyclin D2/cdk4 Activity and Impaired Prb Phosmentioning

confidence: 79%

Early G1 growth arrest of hybridoma B cells by DMSO involves cyclin D2 inhibition and p21[CIP1] induction

et al. 1998

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“…Thus, both forms of pRb co-migrate as the bands indicated by the arrowheads. The faster migrating pRb forms detected in the E1A-cell lysate (marked by asterisks) may represent degradation products or further dephosphorylated forms (Chen et al, 1989). These additional pRb bands are not detected in a reproducible fashion, either alone or in association with E1A (Alevizopoulos et al, 1998; data not shown) Figure 5 The E1A mutants GFP-A3 and DDE-A6 are functional in relieving pRb-mediated repression of E2F transcriptional activity.…”

Section: Effects Of Gfp-a3 and Dde-a6 On Endogenous E2f Activitymentioning

confidence: 94%

Conserved region 2 of adenovirus E1A has a function distinct from pRb binding required to prevent cell cycle arrest by p16INK4a or p27Kip1

Alevizopoulos¹,

Sánchez²,

Amati³

2000

Oncogene

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Ectopic expression of the CDK inhibitors (CKIs) p16 INK4a and p27 Kip1 in Rat1 ®broblasts induces dephosphorylation and activation of Retinoblastoma-family proteins (pRb, p107 and p130), their association with E2F proteins, and cell cycle arrest in G1. The growth-inhibitory action of p16, in particular, is believed to be mediated essentially via pRb activation. The 12S E1A protein of human Adenovirus 5 associates with pRb-family proteins via residues in its Conserved Regions (CR) 1 and 2, in particular through the motif LXCXE in CR2. These interactions are required for E1A to prevent G1 arrest upon co-expression of CKIs. We show here that mutating either of two conserved motifs adjacent to LXCXE in CR2, GFP and SDDEDEE, also impairs the ability of E1A to overcome G1 arrest by p16 or p27. Strikingly, however, these mutations a ect neither the association of E1A with pRb, p07 and p130, nor its ability to derepress E2F-1 transcriptional activity in transient transfection assays. One of the E1A mutants, however, is defective in derepressing several endogenous E2F target genes in the presence of p16 or p27. Thus, CR2 possesses an essential function besides pRb-binding. We speculate that this function might be required for the full derepression of E2F-regulated genes in their natural chromatin context.

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“…The Rb-binding domain of Pura bears some homology to the counterpart domain of T-antigen, although Pura does not possess the LXCXE motif of T-antigen and certain other Rb-binding proteins. Signaling pathways leading to S phase induce the hyperphosphorylation of Rb during G1 (Chen et al, 1989;Lees et al, 1991). Hyperphosphorylation is known to release Rb from binding to a variety of proteins, including those in the E2F family of transcription factors (Chellappan et al, 1991), leading to subsequent activation of several genes involved in aspects of DNA replication (Chittenden et al, 1993;Helin et al, 1993;Kaelin et al, 1992;Shan et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Cell cycle arrest and morphological alterations following microinjection of NIH3T3 cells with Puraα

et al. 1999

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Levels of Pura, a protein implicated in control of both DNA replication and gene transcription,¯uctuate during the cell cycle, being lowest in early S phase and highest just after mitosis. Here we have employed a new video time-lapse technique enabling us to determine the cell cycle position of each cell in an asynchronous culture at a given time and to ask whether introduction of Pura protein at speci®c times can a ect cell cycle progression. Approximately 80% of all NIH3T3 cells injected with Pura were inhibited from passing through mitosis. Cells injected with Pura during S or G2 phases were e ciently blocked with a 4N (G2 phase) DNA level, as determined by quantitative DNA photometry of individual cells. Of the cells injected with Pura during G1 phase, 40% experienced a rapid cell death characterized by extreme cellular fragmentation. Of those G1 injected cells which remained viable, approximately equal numbers were arrested with either 2N or 4N DNA levels. Cells arrested by Pura in G2 phase grew to cover a large surface area. These results link¯uctuations in Pura levels to aspects of cell cycle control.

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Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation

Cited by 915 publications

References 26 publications

Early G1 growth arrest of hybridoma B cells by DMSO involves cyclin D2 inhibition and p21[CIP1] induction

Early G1 growth arrest of hybridoma B cells by DMSO involves cyclin D2 inhibition and p21[CIP1] induction

Conserved region 2 of adenovirus E1A has a function distinct from pRb binding required to prevent cell cycle arrest by p16INK4a or p27Kip1

Cell cycle arrest and morphological alterations following microinjection of NIH3T3 cells with Puraα

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