Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biochem J
2007 Oct 15;4072:277-84. doi: 10.1042/BJ20070064.
Show Gene links
Show Anatomy links
Regulation of neurogenin stability by ubiquitin-mediated proteolysis.
Vosper JM
,
Fiore-Heriche CS
,
Horan I
,
Wilson K
,
Wise H
,
Philpott A
.
???displayArticle.abstract??? NGN (neurogenin), a proneural bHLH (basic helix-loop-helix) transcription factor, plays a central role in promoting neuronal specification and differentiation in many regions of the central nervous system. NGN activity has been shown extensively to be controlled at the transcriptional level. However, in addition, recent findings have indicated that the levels of NGN protein may also be regulated. In the present study, we have demonstrated that NGN protein stability was regulated in both Xenopus embryos and P19 embryonal carcinoma cells, a mammalian neuronal model system. In both systems, NGN was a highly unstable protein that was polyubiquitinated for destruction by the proteasome. NGN binds to DNA in complex with its heterodimeric E-protein partners E12 or E47. We observed that NGN was stabilized by the presence of E12/E47. Moreover, NGN was phosphorylated, and mutation of a single threonine residue substantially reduced E12-mediated stabilization of NGN. Thus E-protein partner binding and phosphorylation events act together to stabilize NGN, promoting its accumulation when it can be active.
Bertrand,
Proneural genes and the specification of neural cell types.
2002, Pubmed
Bertrand,
Proneural genes and the specification of neural cell types.
2002,
Pubmed
Bounpheng,
Degradation of Id proteins by the ubiquitin-proteasome pathway.
1999,
Pubmed
Breitschopf,
A novel site for ubiquitination: the N-terminal residue, and not internal lysines of MyoD, is essential for conjugation and degradation of the protein.
1998,
Pubmed
Ciechanover,
Ubiquitin-mediated proteolysis: biological regulation via destruction.
2000,
Pubmed
Collins,
The proteasome: a utility tool for transcription?
2006,
Pubmed
Doucet,
Multiple phosphorylation events control mitotic degradation of the muscle transcription factor Myf5.
2005,
Pubmed
,
Xenbase
Farah,
Generation of neurons by transient expression of neural bHLH proteins in mammalian cells.
2000,
Pubmed
Furlong,
Vertebrate neurogenin evolution: long-term maintenance of redundant duplicates.
2005,
Pubmed
Glotzer,
Cyclin is degraded by the ubiquitin pathway.
1991,
Pubmed
,
Xenbase
Hershko,
Methylated ubiquitin inhibits cyclin degradation in clam embryo extracts.
1991,
Pubmed
Hofstetter,
Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome.
2005,
Pubmed
Kho,
Degradation of E2A proteins through a ubiquitin-conjugating enzyme, UbcE2A.
1997,
Pubmed
Komuro,
Negative regulation of transforming growth factor-beta (TGF-beta) signaling by WW domain-containing protein 1 (WWP1).
2004,
Pubmed
Lee,
Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein.
1995,
Pubmed
,
Xenbase
Lindon,
Constitutive instability of muscle regulatory factor Myf5 is distinct from its mitosis-specific disappearance, which requires a D-box-like motif overlapping the basic domain.
2000,
Pubmed
Ma,
Identification of neurogenin, a vertebrate neuronal determination gene.
1996,
Pubmed
,
Xenbase
Murray,
Cell cycle extracts.
1991,
Pubmed
Nandi,
The ubiquitin-proteasome system.
2006,
Pubmed
Nguyen,
p27kip1 independently promotes neuronal differentiation and migration in the cerebral cortex.
2006,
Pubmed
Nie,
Notch-induced E2A ubiquitination and degradation are controlled by MAP kinase activities.
2003,
Pubmed
Rashbass,
The DNA-binding protein E12 co-operates with XMyoD in the activation of muscle-specific gene expression in Xenopus embryos.
1992,
Pubmed
,
Xenbase
Ross,
Basic helix-loop-helix factors in cortical development.
2003,
Pubmed
Salic,
Control of beta-catenin stability: reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Shou,
BMPs inhibit neurogenesis by a mechanism involving degradation of a transcription factor.
1999,
Pubmed
Song,
Phosphorylation of nuclear MyoD is required for its rapid degradation.
1998,
Pubmed
Sun,
An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers.
1991,
Pubmed
Tintignac,
Cyclin E-cdk2 phosphorylation promotes late G1-phase degradation of MyoD in muscle cells.
2000,
Pubmed
Vernon,
The cdk inhibitor p27Xic1 is required for differentiation of primary neurones in Xenopus.
2003,
Pubmed
,
Xenbase
Viñals,
BMP-2 decreases Mash1 stability by increasing Id1 expression.
2004,
Pubmed
Yeo,
XNGNR1-dependent neurogenesis mediates early neural cell death.
2005,
Pubmed
,
Xenbase
