Multiple Ser/Thr-rich degrons mediate the degradation of Ci/Gli by the Cul3-HIB/SPOP E3 ubiquitin ligase

Qing Zhang, Qing Shi, Yongbin Chen, Tao Yue, Shuang Li, Bing Wang, Jin Jiang

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

The Cul3-based E3 ubiquitin ligases regulate many cellular processes using a large family of BTB domain-containing proteins as their target recognition components, but how they recognize targets remains unknown. Here we identify and characterize degrons that mediate the degradation of the Hedgehog pathway transcription factor cubitus interruptus (Ci)/Gli by Cul3-Hedghog-induced MATH and BTB domain-containing protein (HIB)/SPOP. Ci uses multiple Ser/Thr (S/T)-rich motifs that bind HIB cooperatively to mediate its degradation. We provide evidence that both HIB and Ci form dimers/oligomers and engage in multivalent interactions, which underlies the in vivo cooperativity among individual HIB-binding sites. We find that similar S/T-rich motifs are present in Gli proteins as well as in numerous HIB-interacting proteins and mediate Gli degradation by SPOP. Our results provide a mechanistic insight into how HIB/SPOP recognizes its substrates and have important implications for the genome-wide prediction of substrates for Cul3-based E3 ligases.

Original languageEnglish (US)
Pages (from-to)21191-21196
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number50
DOIs
StatePublished - Dec 15 2009

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Ubiquitin-Protein Ligases
Proteins
Transcription Factors
Binding Sites
Genome
BTB-POZ Domain
Zinc Finger Protein GLI1

Keywords

  • BTB
  • E3 ligase
  • Gli2
  • Gli3
  • Hedgehog

ASJC Scopus subject areas

  • General

Cite this

Multiple Ser/Thr-rich degrons mediate the degradation of Ci/Gli by the Cul3-HIB/SPOP E3 ubiquitin ligase. / Zhang, Qing; Shi, Qing; Chen, Yongbin; Yue, Tao; Li, Shuang; Wang, Bing; Jiang, Jin.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 50, 15.12.2009, p. 21191-21196.

Research output: Contribution to journalArticle

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AU - Li, Shuang

AU - Wang, Bing

AU - Jiang, Jin

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