Regulation of neurogenin stability by ubiquitin-mediated proteolysis

Jonathan M.D. Vosper , Christelle S. Fiore-Heriche , Ian Horan , Kate Wilson , Helen M. Wise , Anna Philpott (1)

1 Oncology

Neurogenin (NGN), a proneural 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 experiments have indicated that the levels of NGN protein may also be regulated. Here, we demonstrate that NGN protein stability is regulated in both Xenopus embryos and P19 embryonal carcinoma cells, a mammalian neuronal model system. In both systems, NGN is a highly unstable protein that is poly-ubiquitinated for destruction by the proteasome. NGN binds to DNA in complex with its heterodimeric E protein partners E12 or E47. We see that NGN is stabilised by the presence of E12/E47. Moreover, NGN is phosphorylated, and mutation of a single threonine residue substantially reduces E12-mediated stabilisation of NGN. Thus, E-protein partner binding and phosphorylation events act together to stabilise NGN, promoting its accumulation when it can be active.

Mots clés: Life Sciences

Jonathan M.D. Vosper, Christelle S. Fiore-Heriche, Ian Horan, Kate Wilson, Helen M. Wise, et al.. Regulation of neurogenin stability by ubiquitin-mediated proteolysis. Biochemical Journal, 2007, 407 (2), pp.277-284. ⟨10.1042/BJ20070064⟩. ⟨hal-00478736⟩