BMC molecular biology 2009,
PMID: 19435523
Mofunanya, Adaobi; Li, Feng-Qian; Hsieh, Jen-Chih; Takemaru, Ken-Ichi
BACKGROUND
The Wnt/beta-catenin signaling pathway plays crucial roles in embryonic development and in maintenance of organs and tissues in adults. Chibby (Cby) is an evolutionarily conserved molecule that physically interacts with the key downstream coactivator beta-catenin and represses its transcriptional activation potential. Although Cby harbors a predicted coiled-coil motif in the C-terminal region, its molecular nature and functional importance remain largely unexplored.
RESULTS
Here we report that Cby forms a stable complex with itself. Alanine substitutions of two or more of four critical leucine residues within the C-terminal heptad repeats completely eliminate the Cby-Cby interaction. The Cby oligomer predominantly exists as a homodimer. Furthermore, we found that dimerization-deficient Cby mutants still retain the ability to bind to beta-catenin and to repress beta-catenin-dependent gene activation. More importantly, Cby homodimerization is required for its efficient interaction with the nuclear import receptor importin-alpha and subsequent nuclear translocation.
CONCLUSIONS
Our comprehensive mutational analysis of the Cby coiled-coil domain reveals that the four heptad leucine residues play an essential role in mediating Cby homodimerization. Although monomeric Cby is sufficient to bind to beta-catenin and block beta-catenin-mediated transcriptional activation, homodimer formation of Cby is indispensable for its efficient nuclear import.
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Text Mining Data
beta-catenin → Cby: "
Although monomeric
Cby is
sufficient to bind to
beta-catenin and block beta-catenin mediated transcriptional activation, homodimer formation of Cby is indispensable for its efficient nuclear import
"
Manually curated Databases
-
NCI Pathway Database Regulation of nuclear beta catenin signaling and target gene transcription:
beta catenin (CTNNB1)
→
chibby (CBY1)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Regulation of nuclear beta catenin signaling and target gene transcription:
beta catenin (CTNNB1)
→
14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Regulation of nuclear beta catenin signaling and target gene transcription:
beta catenin (CTNNB1)
→
14-3-3 family/chibby/beta catenin complex (YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB-CBY1-CTNNB1)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Regulation of nuclear beta catenin signaling and target gene transcription:
chibby (CBY1)
→
14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Regulation of nuclear beta catenin signaling and target gene transcription:
chibby (CBY1)
→
14-3-3 family/chibby/beta catenin complex (YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB-CBY1-CTNNB1)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Regulation of nuclear beta catenin signaling and target gene transcription:
14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB)
→
14-3-3 family/chibby/beta catenin complex (YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB-CBY1-CTNNB1)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
In total, 45 gene pairs are associated to this article in curated databases