title: Nuclear import factor Srp1 and its associated protein Sts1 couple ribosome-bound nascent polypeptides to proteasomes for cotranslational degradation.
abstract: Cotranslational protein degradation plays an important role in protein quality control and proteostasis. Although ubiquitylation has been suggested to signal cotranslational degradation of nascent polypeptides, cotranslational ubiquitylation occurs at a low level, suggesting the existence of an alternative route for delivery of nascent polypeptides to the proteasome. Here we report that the nuclear import factor Srp1 (also known as importin α or karyopherin α) is required for ubiquitin-independent cotranslational degradation of the transcription factor Rpn4. We further demonstrate that cotranslational protein degradation is generally impaired in the srp1-49 mutant. Srp1 binds nascent polypeptides emerging from the ribosome. The association of proteasomes with polysomes is weakened in srp1-49. The interaction between Srp1 and the proteasome is mediated by Sts1, a multicopy suppressor of srp1-49. The srp1-49 and sts1-2 mutants are hypersensitive to stressors that promote protein misfolding, underscoring the physiological function of Srp1 and Sts1 in degradation of misfolded nascent polypeptides. This study unveils a previously unknown role for Srp1 and Sts1 in cotranslational protein degradation and suggests a novel model whereby Srp1 and Sts1 cooperate to couple proteasomes to ribosome-bound nascent polypeptides.
authors: From the Karmanos Cancer Institute, Department of Oncology, and Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201.
authors: Seung-Wook
authors: SW
authors: Ha
authors: Donghong
authors: D
authors: Ju
authors: Youming
authors: Y
authors: Xie
mesh_terms: D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D028884:Karyopherins / Q000737:chemistry / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D012270:Ribosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination
chemical_list: D004268:DNA-Binding Proteins; D028884:Karyopherins; C119430:RPN4 protein, S cerevisiae; C085810:STS1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C538902:Srp1 protein, S cerevisiae; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex
keywords: Cotranslational Protein Degradation; Nuclear Import Factor Srp1; Proteasome; Protein Degradation; Protein Dynamics; Protein Processing; Protein Turnover; Ubiquitin-independent Degradation