Rb binds c-Jun and activates transcription

Nead, Michael; Baglia, Laurel A.; Antinore, Michael J.; Ludlow, John W.; McCance, Dennis J.

doi:10.1093/emboj/17.8.2342

Cited by 117 publications

(94 citation statements)

References 44 publications

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“…Alternatively, the CMV promoter used to drive E1A expression may be subject to di erential feedback regulation by mutant E1A proteins, particularly those defective in pRB binding. Such a mechanism is plausible given that (1) the CMV promoter contains multiple AP-1 cis-elements (Prestridge, 1991; Reddy et al, 1995 and references therein) and (2) such elements have been shown to be targets of pRB regulation in the context of other promoters (Robbins et al, 1990;Nead et al, 1998;Nishitani et al, 1999, and this study). Irrespective, all mutants displayed the expected speci®city as shown in the upper panels of Figure 2.…”

Section: Construction Of a Panel Of E1a 12s Mutants Deficient In Cellmentioning

confidence: 72%

“…Because pRB has been reported to directly interact with other transcription factors including members of the E2F family (reviewed by Nevins et al, 1997), MyoD (Gu et al, 1993), members of the CCAAT/enhancer ± binding protein (C/EBP) family (Chen et al, 1996a,b), and, in particular, cJun and c-Fos (Nead et al, 1998;Nishitani et al, 1999), we considered the possibility that pRB may similarly interact with c-Fos in AKR-2B ®broblasts. Although in vitro transcribed and translated c-Fos has been shown to interact with the B pocket region of pRB fused to glutathione-S-transferase via`pull down' assay (Nead et al, 1998), we were unable to detect such an interaction between c-Fos and full-length pRB by co-immunoprecipitation experiments conducted with AKR-2B ®broblast extracts and a variety antibodies recognizing di erent c-Fos and pRB epitopes (data not shown). Thus, our data do not support a model in which c-Fos and pRB cooperate through direct physical interaction at least in AKR-2B extracts.…”

Section: Discussionmentioning

confidence: 99%

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The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent mouse tissue factor promoter in fibroblasts

et al. 2000

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Serum-stimulation of quiescent mouse ®broblasts results in transcriptional activation of tissue factor (TF), the cellular initiator of blood coagulation. This requires the rapid entry of c-Fos into speci®c AP-1 DNA-binding complexes and can be strongly inhibited by the adenovirus E1A 12S gene product. In this study, we utilized a panel of E1A mutants de®cient in cellular protein binding to analyse the molecular basis for E1A inhibition of a minimal, c-Fos-dependent TF promoter/ reporter construct in mouse AKR-2B ®broblasts. Mutations which impaired binding of the retinoblastoma tumor suppressor protein family members pRB, p107, and p130 relieved E1A-mediated inhibition of transcription in response to serum-stimulation or c-Fos overexpression. Inhibition was restricted to the G 0 to G 1 transition, consistent with the speci®city of E1A for hypophosphorylated forms of RB proteins. Although E1A mutants de®cient in CBP/p300 binding retained the ability to inhibit TF transcription, deletion of the aminoterminal portion of the CBP/p300 interaction domain was required to permit rescue of TF promoter activity by coexpression of pRB. Moreover, ectopic p107 could e ectively substitute for pRB in relieving E1A-mediated repression. In primary mouse embryo ®broblasts, activity of the minimal AP-1-dependent TF promoter was suppressed in Rb 7/7 cells compared to parallel Rb +/7 and Rb +/+ transfectants. Ectopic expression of either pRB or p107 markedly enhanced TF promoter activity in Rb 7/7 ®broblasts. Collectively, these data imply that pRB and p107 can cooperate with c-Fos to activate TF gene transcription in ®broblasts and suggest a requirement for another, as yet unidenti®ed, E1A-binding protein. Oncogene (2000) 19, 3352 ± 3362.

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Section: Construction Of a Panel Of E1a 12s Mutants Deficient In Cellmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent mouse tissue factor promoter in fibroblasts

et al. 2000

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“…During adipocyte differentiation, an interaction between Rb and members of the C/EBP family of transcription factors occurs that potentiates C/EBP DNA binding and transcriptional activity (Chen et al 1996). In terminally differentiating keratinocytes, Rb interacts with c-Jun and stimulates its transcriptional activity (Nead et al 1998).…”

Section: P21 P57 and Rb Function In Muscle Development At The Myogementioning

confidence: 99%

p21CIP1 and p57KIP2 control muscle differentiation at the myogenin step

Zhang¹,

Wong²,

Liu³

et al. 1999

Genes & Development

360

332

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Cell-cycle arrest is thought to be required for differentiation of muscle cells. However, the molecules controlling cell-cycle exit and the differentiation step(s) dependent on cell-cycle arrest are poorly understood. Here we show that two Cdk inhibitors, p21 CIP1 and p57 KIP2 , redundantly control differentiation of skeletal muscle and alveoli in the lungs. Mice lacking both p21 and p57 fail to form myotubes, display increased proliferation and apoptotic rates of myoblasts, and display endoreplication in residual myotubes. This point of arrest during muscle development is identical to that of mice lacking the myogenic transcription factor myogenin, indicating a role for cell-cycle exit in myogenin function. Expression of myogenin, p21, and p57 is parallel but independent, and in response to differentiation signals, these proteins are coordinately regulated to trigger both cell-cycle exit and a dependent muscle-specific program of gene expression to initiate myoblast terminal differentiation and muscle formation. Embryonic development is a complex process that requires precise spatial and temporal control of cell proliferation coordinated together with differentiation, morphogenesis, and pattern formation. Cell proliferation in the embryo is controlled by an intricate network of signal transduction pathways that integrate growth regulatory signals through regulation of cyclin-dependent kinases (Cdks), a family of enzymes that catalyze events required for cell-cycle transitions. Primary targets for this regulation are the G 1 cyclin/Cdk complexes cyclin D/Cdk4 and cyclin E/Cdk2, which cooperate to control the G 1 → S transition through phosphorylation and inactivation of the retinoblastoma (Rb) protein. Among other functions, Rb acts as a transcriptional repressor of E2F-regulated genes important for cell proliferation (Weinberg 1995). A large number of regulatory mechanisms exist to modulate Cdk activity, reflecting the complexity of the signaling pathways involved and the necessity to precisely control proliferation for the development of an organism. A particularly versatile mechanism for developmental control is the inhibition of Cdks by cyclin-dependent kinase inhibitors (CKIs), of which there are two families: the p16 INK4a family, including p15, p16, p18, and p19; and the p21 CIP1/WAF1 family, including p21, p27, and p57 (Harper and Elledge 1996). The p16 family specifically inhibits Cdk4 and Cdk6, whereas the p21 family inhibits all Cdks involved in G 1 /S transition. The roles of these CKIs in development and in cancer have been revealed through targeted gene inactivation in mice. Although CKIs show striking tissuespecific patterns of expression during development, surprisingly only p57 loss has been shown to have a significant role in multiple tissues during embryonic development, suggesting that the other inhibitors are either not required or are redundant. Loss of p57 in humans results in the complex overgrowth and cancer predisposition disease Beckwith-Wiedemann syndrome (Zhang et al. 1997).A variety...

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“…Thus, leucine zippers may interact with other structural entities, too. Indeed, Par-4 itself can interact with zinc ®ngers of WT1 (Johnstone et al, 1996) and PKCx, and l/i (Diaz- Meco et al, 1996), fos can bind to the pocket domain of Rb (Nead et al, 1998), and ATF1 can interact with the catalytic subunit of protein kinase CKII (Yamaguchi et al, 1998).…”

Section: The Leucine Zipper As Interaction Domain In Transcription Famentioning

confidence: 99%

Interaction partners of Dlk/ZIP kinase: co-expression of Dlk/ZIP kinase and Par-4 results in cytoplasmic retention and apoptosis

et al. 1999

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Dlk/ZIP kinase is a newly discovered serine/threonine kinase which, due to its homology to DAP kinase, was named DAP like kinase, Dlk. This kinase is tightly associated with nuclear structures, it undergoes extensive autophosphorylation and phosphorylates myosin light chain and core histones H3, H2A and H4 in vitro. Moreover, it possesses a leucine zipper which mediates interaction with transcription factor ATF-4, therefore it was called ZIP kinase. We employed the yeast twohybrid system to identify interaction partners of Dlk that might serve as regulators or targets. Besides ATF-4 and others we found Par-4, a modulator of transcription factor WT1 and mediator of apoptosis. Complex formation between Dlk and Par-4 was con®rmed by GST pull-down experiments and kinase reactions in vitro and coexpression experiments in vivo. The interaction domain within Dlk was mapped to an arginine-rich region between residues 338 ± 417, rather than to the leucine zipper. Strikingly, coexpression of Dlk and Par-4 lead to relocation of Dlk from the nucleus to the cytoplasm, particularly to actin ®laments. These interactions provoked a dramatic reorganization of the cytoskeleton and morphological symptoms of apoptosis, thus suggesting a functional relationship between Dlk and Par-4 in the control of apoptosis.

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Rb binds c-Jun and activates transcription

Cited by 117 publications

References 44 publications

The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent mouse tissue factor promoter in fibroblasts

The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent mouse tissue factor promoter in fibroblasts

p21CIP1 and p57KIP2 control muscle differentiation at the myogenin step

Interaction partners of Dlk/ZIP kinase: co-expression of Dlk/ZIP kinase and Par-4 results in cytoplasmic retention and apoptosis

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