Nuclear Import Factor Srp1 and Its Associated Protein Sts1 Couple Ribosome-bound Nascent Polypeptides to Proteasomes for Cotranslational Degradation

作者：Ha Seung Wook; Ju Donghong; Xie Youming^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289(5): 2701-2710.

DOI：10.1074/jbc.M113.524926

• Proteasome
• Protein Degradation
• Protein Dynamics
• Protein Processing
• Protein Turnover
• Cotranslational Protein Degradation
• Nuclear Import Factor Srp1
• Ubiquitin-independent Degradation

Background: The mechanism underlying cotranslational protein degradation remains poorly understood. Results: The nuclear import factor Srp1 binds ribosome-bound nascent polypeptides. Sts1 mediates the interaction between Srp1 and the proteasome. Conclusion: Srp1 and Sts1 couple proteasomes to nascent polypeptides emerging from the ribosome for cotranslational degradation. Significance: This study unveils a novel role for Srp1 and Sts1 in cotranslational protein degradation.
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 or karyopherin ) 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.

• 出版日期2014-1-31