The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest

Dunaief, Joshua L.; Strober, Bruce; Guha, Sushovan; Khavari, Paul A.; Alin, Kimona; Luban, Jeremy; Begemann, Martin; Crabtree, Gerald R.; Goff, Stephen P.

doi:10.1016/0092-8674(94)90405-7

Cited by 597 publications

(609 citation statements)

References 53 publications

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“…BRG1 interacts with the unphosphorylated pocket domain, and in BRG1-deficient cells its reexpression is capable of conferring a growth arrested, flat cell phenotype (Dunaief et al, 1994). However, it has since been shown that the Rb-binding site of BRG1 is not conserved in the Drosophila BRG homolog, and mutation of human BRG1 so that it could no longer bind Rb did not affect its ability to arrest cells in G1, suggesting that the genetic interaction between BRG1 and Rb does not reflect a direct biochemical interaction.…”

Section: Mechanisms Of Transcriptional Controlmentioning

confidence: 99%

Retinoblastoma family genes

2006

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Section: Mechanisms Of Transcriptional Controlmentioning

confidence: 99%

Retinoblastoma family genes

2006

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“…These proteins are ATPases, central components of the human SWI-SNF nucleosome-remodeling complex, which is involved in global transcriptional activation because of its ability to bind DNA, disrupt nucleosomes, and provide transcription factors with access to nucleosomal DNA (Zhang et al, 2000). Previous studies have suggested that SWI-SNF activity may be important for Rb-related growth suppression, and this is dependent on Rb binding to BRG1 at the core of the SWI-SNF complex (Dunaief et al, 1994). Furthermore, the role of SWI-SNF in Rb growth suppression appears linked, at least in part, to the ability of Rb to efficiently recruit HDAC-1 and -3 (Dahiya et al, 2001).…”

Section: Molecular Studiesmentioning

confidence: 99%

Cell cycle control and beyond: emerging roles for the retinoblastoma gene family

et al. 2006

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Rb family proteins (pRb/p105, Rb2/p130 and p107) play a key role in cell cycle control and are worthily involved in transcription repression and tumor suppression. The mechanisms of transcriptional activation and repression by the Rb gene family has been extensively investigated: pRb, pRb2/p130 and p107 interact with different E2F family factors and can inhibit E2F responsive promoters, interfering with progression of cell cycle, gene transcription, initiation of apoptotic process and cell differentiation. Recent studies have indicated that Rb and Rb2/p130 may be involved in cellular response to DNA damage events, by influencing the transcription of factors involved in DNA repair pathways. In particular, evidences suggest that Rb loss and target gene deregulation impacts on the repair of UV-induced pyrimidine pyrimidone photoproducts (6-4 PP) by regulating the expression of several DNA damage factors involved in UV DNA damage repair processes, including proliferating cell nuclear antigen. Ongoing studies are focused on the mechanisms by which Rb family genes drive cell cycle exit following DNA damage induction, and how Rb gene family's interaction with chromatin remodeling factors can influence DNA repair dynamics.

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“…Western blot analysis employing an antibody speci®c for the hypophosphorylated form of pRb (Dunaef et al, 1994) revealed marked pRb dephosphorylation in response to HMBA, and, to a considerably lesser extent, to 1 mM SAHA (Figure 3a). Cells exposed to 2.5 mM SAHA displayed a prominent dephosphorylated pRB species migrating at *65 kDa, suggestive of a pRB cleavage product.…”

Section: Saha Induces Prb Dephosphorylation and Cleavage And Extensimentioning

confidence: 99%

Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-XL, c-Jun, and p21CIP1, but independent of p53

et al. 1999

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Determinants of di erentiation and apoptosis in myelomonocytic leukemia cells (U937) exposed to the novel hybrid polar compound SAHA (suberoylanilide hydroxamic acid) have been examined. In contrast to hexamethylenbisacetamide (HMBA), SAHA-related maturation was limited and accompanied by marked cytoxicity. SAHA-mediated apoptosis occurred within the G 0 G 1 and S phase populations, and was associated with decreased mitochondrial membrane potential, caspase-3 activation, PARP degradation, hypophosphorylation/cleavage of pRB, and down-regulation of c-Myc, c-Myb, and B-Myb. Enforced expression of Bcl-2 or Bclx L inhibited SAHA-induced apoptosis, but only modestly potentiated di erentiation. While SAHA induced the cyclin-dependent kinase inhibitor p21 CIP1 , antisense ablation of this CDKI increased, rather than decreased, SAHA-related lethality. In contrast, conditional expression of wild-type p53 failed to modify SAHA actions, but markedly potentiated HMBA-induced apoptosis. Finally, SAHA modestly increased expression/activation of the stress-activated protein kinase (SAPK/JNK); moreover, SAHA-related lethality was partially attenuated by a dominant-negative c-Jun mutant protein (TAM67). SAHA did not stimulate mitogen-activated protein kinase (MAPK), nor was lethality diminished by the speci®c MEK/MAPK inhibitor PD98059. These ®ndings indicate that SAHA potently induces apoptosis in human leukemia cells via a pathway that is p53-independent but at least partially regulated by Bcl-2/Bcl-x L , p21 CIP1 , and the c-Jun/AP-1 signaling cascade.

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The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest

Cited by 597 publications

References 53 publications

Retinoblastoma family genes

Retinoblastoma family genes

Cell cycle control and beyond: emerging roles for the retinoblastoma gene family

Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-XL, c-Jun, and p21CIP1, but independent of p53

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