Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 70, Issue 8, Pages 1439-1450Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-012-1215-y
Keywords
Initiation; eIF6; PKC beta; 40S; Asc1p
Categories
Funding
- AIRC (Associazione Italiana Ricerca sul Cancro) [IG11390]
- AICR (Association for International Cancer Research, UK) [09-0061]
- TELETHON [GGP05043]
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The receptor for activated C-kinase 1 (RACK1) is a conserved structural protein of 40S ribosomes. Strikingly, deletion of RACK1 in yeast homolog Asc1 is not lethal. Mammalian RACK1 also interacts with many nonribosomal proteins, hinting at several extraribosomal functions. A knockout mouse for RACK1 has not previously been described. We produced the first RACK1 mutant mouse, in which both alleles of RACK1 gene are defective in RACK1 expression (Delta F/Delta F), in a pure C57 Black/6 background. In a sample of 287 pups, we observed no Delta F/Delta F mice (72 expected). Dissection and genotyping of embryos at various stages showed that lethality occurs at gastrulation. Heterozygotes (Delta F/+) have skin pigmentation defects with a white belly spot and hypopigmented tail and paws. Delta F/+ have a transient growth deficit (shown by measuring pup size at P11). The pigmentation deficit is partly reverted by p53 deletion, whereas the lethality is not. Delta F/+ livers have mild accumulation of inactive 80S ribosomal subunits by polysomal profile analysis. In Delta F/+ fibroblasts, protein synthesis response to extracellular and pharmacological stimuli is reduced. These results highlight the role of RACK1 as a ribosomal protein converging signaling to the translational apparatus.
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