Loss of function of the tumor suppressor DKC1 perturbs p27 translation control and contributes to pituitary tumorigenesis.

ABSTRACT: Mutations in DKC1, encoding for dyskerin, a pseudouridine synthase that modifies rRNA and regulates telomerase activity, are associated with ribosomal dysfunction and increased cancer susceptibility in the human syndrome, X-linked dyskeratosis congenita (X-DC). In a mouse model for X-DC, impairments in DKC1 function affected the translation of specific mRNAs harboring internal ribosomal entry site (IRES) elements, including the tumor suppressor, p27. However, how this translational deregulation contributes to tumor initiation and progression remains poorly understood. Here, we report that impairment in p27 IRES-mediated translation due to decreased levels of DKC1 activity markedly increases spontaneous pituitary tumorigenesis in p27 heterozygous mice. Using a new bioluminescent mouse model

SUBMITTER: Bellodi C 

PROVIDER: S-EPMC2913864 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature