Retinoblastoma protein partners

Morris, Erick; Dyson, Nicholas J.

doi:10.1016/s0065-230x(01)82001-7

Cited by 318 publications

(266 citation statements)

References 184 publications

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“…These results further suggest that Rb has antiapoptotic effects independent of its ability to regulate gene expression. As proteins reported to interact with Rb such as c-Jun N-terminal kinase and c-ABL (Morris and Dyson, 2001;Chau and Wang, 2003) can also induce apoptosis, it is possible that their interaction with Rb might also be able to inhibit their pro-apoptotic signaling. Interestingly, the caspase-resistant form of Rb is unable to prevent DNA-damage-induced apoptosis, suggesting that in addition to cell type, the role of Rb in suppressing apoptosis may depend on the apoptotic stimulus.…”

Section: Cell Cycle Roles Of the Rb Family Of Proteinsmentioning

confidence: 99%

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Retinoblastoma family genes

2006

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Section: Cell Cycle Roles Of the Rb Family Of Proteinsmentioning

confidence: 99%

“…These functions of Rb are mediated by its interaction with a large number of cellular proteins. Currently, over 100 proteins have been reported to interact with the Rb protein (Morris and Dyson, 2001), and most, if not all, of these interactions also involve the pocket domain. The best-studied binding partners of Rb are the E2F transcription factors.…”

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confidence: 99%

Retinoblastoma family genes

2006

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“…There is also evidence that Rb has a role in cell fate specification [9][10][11] . In support of this notion, Rb can bind more than 110 different proteins, several of which are tissue-restricted transcription factors 12 . It is conceivable that Rb binds to E2F and regulates cell cycle exit through its canonical pathway and then contributes to cell fate specification, differentiation or both through interactions with tissuerestricted transcription factors.…”

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confidence: 93%

Rb regulates proliferation and rod photoreceptor development in the mouse retina

et al. 2004

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In the mouse, the seven main classes of retinal cell types (rod, cone, bipolar, horizontal, amacrine, ganglion and Müller glial cells) are produced from multipotent progenitor cells over a 17-d interval starting at embryonic day (E) 11.5 and continuing through postnatal day (P) 9. The overall size of the retina and the proportion of each cell type contained therein is essential for proper visual processing; therefore, during retinal development, cell cycle exit and cell fate specification are coordinated to ensure that the adult retina forms appropriately 1,2 . When cell proliferation and cell fate specification become uncoupled, as in retinoblastoma 3 , microphthalmia 4,5 and some forms of retinal dysplasia 6,7 and degeneration 8 , vision is severely compromised. By studying individual proteins that integrate the decision to exit the cell cycle and to specify cell fate, we may begin to gain insights into the synchronization of these two important processes during neural development.Rb lies at the heart of the regulatory network that executes cell cycle exit during the G1 phase through interactions with the E2F transcription factor family. There is also evidence that Rb has a role in cell fate specification [9][10][11] . In support of this notion, Rb can bind more than 110 different proteins, several of which are tissue-restricted transcription factors 12 . It is conceivable that Rb binds to E2F and regulates cell cycle exit through its canonical pathway and then contributes to cell fate specification, differentiation or both through interactions with tissuerestricted transcription factors.To overcome the embryonic lethality of Rb1 -/-embryos, which die in utero around E13.5, we used an explant culture procedure to study the development of isolated whole retinas beyond E13.5. To complement and extend the explant culture studies in vivo, we inactivated the gene Rb1 in the retina by using a new tissue-specific Cre transgenic line (Chx10-cre) crossed to Rb1 lox mice. Finally, we injected a Cre-expressing replication-incompetent retrovirus into the eyes of newborn Rb1 lox mice to generate clones of cells lacking Rb. These experiments showed that Rb is required in a cell-autonomous manner for appropriate cell cycle exit and rod development in the mouse retina. This is the first example of a cell-autonomous role for an Rb family member in these two interrelated processes in the developing retina. RESULTS Rb expression during developmentTo identify the cells expressing Rb in the developing mouse retina, we immunolabeled retinal cryosections at six postnatal stages of development (P0, P3, P6, P9, P12 and P21). At P0, when approximately 35% of cells are still dividing and 65% are postmitotic 1,13 (R. Martins and M.A.D., unpublished results), Rb was expressed in the nuclei of dividing retinal progenitor cells in the outer neuroblastic layer and postmitotic differentiating neurons in the developing inner nuclear layer (Fig. 1a-d). To verify that the cells expressing Rb in the outer neuroblastic layer were actively dividin...

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“…Identification of the protein interaction motifs within E1A and determination of the specific residues involved in intermolecular contacts have identified a number of MoRFs that are also present in cellular proteins. These include the PXDLS (where X is a variable) motif that binds the transcriptional corepressor CtBP (Chinnadurai, 2002), the LXCXE motif that binds the cell cycle regulator pRb (Morris and Dyson, 2001), the PXLXP motif that binds the BS69 corepressor (Ansieau and Leutz, 2002) and the FXD/EXXXL motif that binds CBP/p300 acetyltransferases (O'Connor et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Identification of a molecular recognition feature in the E1A oncoprotein that binds the SUMO conjugase UBC9 and likely interferes with polySUMOylation

et al. 2010

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Hub proteins have central roles in regulating cellular processes. By targeting a single cellular hub, a viral oncogene may gain control over an entire module in the cellular interaction network that is potentially comprised of hundreds of proteins. The adenovirus E1A oncoprotein is a viral hub that interacts with many cellular hub proteins by short linear motifs/molecular recognition features (MoRFs). These interactions transform the architecture of the cellular protein interaction network and virtually reprogram the cell. To identify additional MoRFs within E1A, we screened portions of E1A for their ability to activate yeast pseudohyphal growth or differentiation. This identified a novel functional region within E1A conserved region 2 comprised of the sequence EVIDLT. This MoRF is necessary and sufficient to bind the N-terminal region of the SUMO conjugase UBC9, which also interacts with SUMO noncovalently and is involved in polySUMOylation. Our results suggest that E1A interferes with polySUMOylation, but not with monoSUMOylation. These data provide the first insight into the consequences of the interaction of E1A with UBC9, which was initially described in 1996. We further demonstrate that polySUMOylation regulates pseudohyphal growth and promyelocytic leukemia body reorganization by E1A. In conclusion, the interaction of the E1A oncogene with UBC9 mimics the normal binding between SUMO and UBC9 and represents a novel mechanism to modulate polySUMOylation.

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Retinoblastoma protein partners

Cited by 318 publications

References 184 publications

Retinoblastoma family genes

Retinoblastoma family genes

Rb regulates proliferation and rod photoreceptor development in the mouse retina

Identification of a molecular recognition feature in the E1A oncoprotein that binds the SUMO conjugase UBC9 and likely interferes with polySUMOylation

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