DNAJB6 chaperones PP2A mediated dephosphorylation of GSK3β to downregulate β-catenin transcription target, osteopontin.

ABSTRACT: Elevated levels of the oncoprotein, osteopontin (OPN), are associated with poor outcome of several types of cancers including melanoma. We have previously reported an important involvement of DNAJB6, a member of heat-shock protein 40 (HSP40) family, in negatively impacting tumor growth. The current study was prompted by our observations reported here which revealed a reciprocal relationship between DNAJB6 and OPN in melanoma specimens. The 'J domain' is the most conserved domain of HSP40 family of proteins. Hence, we assessed the functional role of the J domain in activities of DNAJB6. We report that the J domain of DNAJB6 is involved in mediating OPN suppression. Deletion of the J domain renders DNAJB6 incapable of impeding malignancy and suppressing OPN. Our mechanistic investigations re

SUBMITTER: Mitra A 

PROVIDER: S-EPMC3717376 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature