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Jia, J., Zhang, L., Zhang, Q., Tong, C., Wang, B., Hou, F., Amanai, K., Jiang, J. (2005). Phosphorylation by double-time/CKI epsilon and CKI alpha targets Cubitus interruptus for slimb/beta-TRCP-mediated proteolytic processing.  Dev. Cell 9(6): 819--830.
FlyBase ID
FBrf0190207
Publication Type
Research paper
Abstract

Hedgehog (Hh) proteins govern animal development by regulating the Gli/Ci family of transcription factors. In Drosophila, Hh signaling blocks proteolytic processing of full-length Ci to generate a truncated repressor form. Ci processing requires sequential phosphorylation by PKA, GSK3, and a casein kinase I (CKI) family member(s). Here we show that Double-time (DBT)/CKIepsilon and CKIalpha act in conjunction to promote Ci processing. CKI phosphorylates Ci at three clusters of serine residues primed by PKA and GSK3 phosphorylation. CKI phosphorylation of Ci confers binding to the F-box protein Slimb/beta-TRCP, the substrate recognition component of the SCF(Slimb/beta-TRCP) ubiquitin ligase required for Ci processing. CKI phosphorylation sites act cooperatively to promote Ci processing in vivo. Substitution of Ci phosphorylation clusters with a canonical Slimb/beta-TRCP recognition motif in beta-catenin renders Slimb/beta-TRCP binding and Ci processing independent of CKI. We propose that phosphorylation of Ci by CKI creates multiple Slimb/beta-TRCP binding sites that act cooperatively to recruit SCF(Slimb/beta-TRCP).

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Dev. Cell
    Title
    Developmental Cell
    Publication Year
    2001-
    ISBN/ISSN
    1534-5807 1878-1551
    Data From Reference
    Alleles (36)
    Gene Groups (1)
    Genes (19)
    Physical Interactions (1)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (4)
    Transgenic Constructs (25)