Format

Send to

Choose Destination
Mol Cell Biol. 2017 Jan 19;37(3). pii: e00279-16. doi: 10.1128/MCB.00279-16. Print 2017 Feb 1.

Asc1p/RACK1 Connects Ribosomes to Eukaryotic Phosphosignaling.

Author information

1
Department of Microbiology and Genetics and Göttingen Center for Molecular Biosciences (GZMB), Georg-August University, Göttingen, Germany.
2
Department of Molecular Structural Biology and Göttingen Center for Molecular Biosciences (GZMB), Georg-August University, Göttingen, Germany.
3
Department of Microbiology and Genetics and Göttingen Center for Molecular Biosciences (GZMB), Georg-August University, Göttingen, Germany ovaleri@gwdg.de.

Abstract

WD40 repeat proteins fold into characteristic β-propeller structures and control signaling circuits during cellular adaptation processes within eukaryotes. The RACK1 protein of Saccharomyces cerevisiae, Asc1p, consists exclusively of a single seven-bladed β-propeller that operates from the ribosomal base at the head region of the 40S subunit. Here we show that the R38D K40E ribosomal binding-compromised variant (Asc1DEp) is severely destabilized through mutation of phosphosite T143 to a dephosphorylation-mimicking alanine, probably through proteasomal degradation, leading to asc1- phenotypes. Phosphosite Y250 contributes to resistance to translational inhibitors but does not influence Asc1DEp stability. Beyond its own phosphorylation at T143, Y250, and other sites, Asc1p heavily influences the phosphorylation of as many as 90 proteins at 120 sites. Many of these proteins are regulators of fundamental processes ranging from mRNA translation to protein transport and turnover, cytoskeleton organization, and cellular signaling. Our data expose Asc1p/RACK1 as a key factor in phosphosignaling and manifest it as a control point at the head of the ribosomal 40S subunit itself regulated through posttranslational modification.

KEYWORDS:

Asc1/RACK1; Saccharomyces cerevisiae; protein phosphorylation; quantitative proteomics; ribosome; signal transduction network

PMID:
27821475
PMCID:
PMC5247610
DOI:
10.1128/MCB.00279-16
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center