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Citation
Zhang, Q., Shi, Q., Chen, Y., Yue, T., Li, S., Wang, B., Jiang, J. (2009). Multiple Ser/Thr-rich degrons mediate the degradation of Ci/Gli by the Cul3-HIB/SPOP E3 ubiquitin ligase.  Proc. Natl. Acad. Sci. U.S.A. 106(50): 21191--21196.
FlyBase ID
FBrf0215181
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC2795488 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Proc. Natl. Acad. Sci. U.S.A.
    Title
    Proceedings of the National Academy of Sciences of the United States of America
    Publication Year
    1915-
    ISBN/ISSN
    0027-8424
    Data From Reference
    Alleles (7)
    Genes (4)
    Physical Interactions (9)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (2)
    Transgenic Constructs (5)