Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P51532 (
transcriptional activator
)
6,546
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Siah-interacting protein (SIP) was identified as a novel adaptor that physically links the E3 ubiquitin ligase activity of Siah-1 with Skp1 and Ebi F-Box protein in the degradation of beta-catenin, a
transcriptional activator
of TCF/LEF genes. In this study, we have used solution NMR spectroscopy to characterize the domain structure of
SIP
, which includes a novel helical hairpin domain at the N-terminus flexibly linked to a CS domain and an unstructured carboxy terminal SGS domain. These studies have been complemented by mapping the sites of functionally important protein-protein interactions involving Siah-1 and Skp1 to individual domains of
SIP
. NMR-based chemical shift perturbation assays show that Siah-1 interacts with the flexible linker between
SIP
N and CS domains. This site for interaction in the linker does not perturb residues in the structured region at the N-terminus but does appear to restrict the rotational freedom of the
SIP
CS domain in the context of the full-length protein. In contrast, Skp1 engages the
SIP
CS domain exclusively through weak interactions that are not coupled to the other domains. The principal role of the modular structure of
SIP
appears to be in bringing these two proteins into physical proximity and orchestrating the orientation required for polyubiquitination of beta-catenin in the intact SCF-type complex.
...
PMID:The modular structure of SIP facilitates its role in stabilizing multiprotein assemblies. 1599 1
