N-Myc is a downstream target of RET signaling and is required for transcriptional regulation of p18(Ink4c) by the transforming mutant RET(C634R).

ABSTRACT: Inherited activating mutations in RET predispose humans to Multiple Endocrine Neoplasia type-2 (MEN2). The MEN2A-specific mutation RET(C634R), RET2A, has been shown to simultaneously downregulate the CDKIs p18 and p27, and upregulate cyclin D1. Importantly, the loss of p18 is necessary and sufficient for RET2A-mediated hyperproliferation. The loss of N-Myc in mice results in embryonic lethality due to a lack of neuronal progenitor cells that fail to proliferate, correlate with accumulation of p18 and p27. Therefore, N-Myc may regulate expression of both CDKIs. Also, N-Myc is expressed predominantly in neuroendocrine cells that give rise to the primary cell types affected in MEN2A. Together these studies suggest that N-Myc is a downstream target of RET2A signaling that prevents accumulation

SUBMITTER: Kulkarni MV 

PROVIDER: S-EPMC5528269 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature