Ter94 ATPase complex targets k11-linked ubiquitinated ci to proteasomes for partial degradation

Zhao Zhang; Xiangdong Lv; Wen-chi Yin; Xiaoyun Zhang; Jing Feng; Wenqing Wu; Chi-chung Hui; Lei Zhang; Yun Zhao

doi:10.1016/j.devcel.2013.05.006

Ter94 ATPase complex targets k11-linked ubiquitinated ci to proteasomes for partial degradation

Dev Cell. 2013 Jun 24;25(6):636-44. doi: 10.1016/j.devcel.2013.05.006. Epub 2013 Jun 6.

Authors

Zhao Zhang¹, Xiangdong Lv, Wen-chi Yin, Xiaoyun Zhang, Jing Feng, Wenqing Wu, Chi-chung Hui, Lei Zhang, Yun Zhao

Affiliation

¹ State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

PMID: 23747190
DOI: 10.1016/j.devcel.2013.05.006

Abstract

The Cubitus interruptus (Ci)/Gli family of transcription factors can be degraded either completely or partially from a full-length form (Ci155/Gli(FL)) to a truncated repressor (Ci75/Gli(R)) by proteasomes to mediate Hedgehog (Hh) signaling. The mechanism by which proteasomes distinguish ubiquitinated Ci/Gli to carry out complete versus partial degradation is not known. Here, we show that Ter94 ATPase and its mammalian counterpart, p97, are involved in processing Ci and Gli3 into Ci75 and Gli3(R), respectively. Ter94 regulates the partial degradation of ubiquitinated Ci by Cul1-Slimb-based E3 ligase through its adaptors Ufd1-like and dNpl4. We demonstrate that Cul1-Slimb-based E3 ligase, but not Cul3-Rdx-based E3 ligase, modifies Ci by efficient addition of K11-linked ubiquitin chains. Ter94(Ufd1-like/dNpl4) complex interacts directly with Cul1-Slimb, and, intriguingly, it prefers K11-linked ubiquitinated Ci. Thus, Ter94 ATPase and K11-linked ubiquitination in Ci contribute to the selectivity by proteasomes for partial degradation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases / genetics
Adenosine Triphosphatases / metabolism*
Animals
Carrier Proteins / genetics
Carrier Proteins / metabolism
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
Cells, Cultured
Cullin Proteins / genetics
Cullin Proteins / metabolism
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Drosophila Proteins / genetics
Drosophila Proteins / metabolism*
Drosophila melanogaster
Hedgehog Proteins / genetics
Hedgehog Proteins / metabolism
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism
Proteasome Endopeptidase Complex / genetics
Proteasome Endopeptidase Complex / metabolism*
Protein Binding / physiology
Signal Transduction / physiology
Smad Proteins, Inhibitory / genetics
Transcription Factors / genetics
Transcription Factors / metabolism*
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism
Ubiquitination / physiology
Valosin Containing Protein

Substances

Carrier Proteins
Cell Cycle Proteins
Cullin 1
Cullin Proteins
DNA-Binding Proteins
Drosophila Proteins
Hedgehog Proteins
Intracellular Signaling Peptides and Proteins
Rdx protein, Drosophila
Roc1a protein, Drosophila
Smad Proteins, Inhibitory
Transcription Factors
ci protein, Drosophila
slmb protein, Drosophila
Ubiquitin-Protein Ligases
Proteasome Endopeptidase Complex
Adenosine Triphosphatases
Valosin Containing Protein
ter94 protein, Drosophila