SAG/RBX2 E3 ligase complexes with UBCH10 and UBE2S E2s to ubiquitylate β-TrCP1 via K11-linkage for degradation.

ABSTRACT: SAG/RBX2 and RBX1 are two family members of RING components of Cullin-RING ligases (CRLs), required for their enzymatic activity. Previous studies showed that SAG prefers to bind with CUL5, as well as CUL1, whereas RBX1 binds exclusively to CULs1-4. Detailed biochemical difference between SAG and RBX1, and whether SAG mediates cross-talk between CRL5 and CRL1 are previously unknown. Here we report that the levels of SAG and β-TrCP1 are inversely correlated, and SAG-CUL5-βTrCP1 forms a complex under physiological condition. SAG-CUL5, but not RBX1-CUL1, negatively modulates β-TrCP1 levels by shortening its protein half-life through promoting its ubiquitylation via atypical K11-linkage. Consistently, chemical inducers of SAG reduced β-TrCP1 level. Furthermore, SAG mainly binds to E2s UBCH10 a

SUBMITTER: Kuang P 

PROVIDER: S-EPMC5133542 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature