The CDC37-HSP90 chaperone complex co-translationally degrades the nascent kinase-dead mutant of HIPK2

Homeodomain-interacting protein kinase 2 (HIPK2) is a highly conserved, constitutively active Ser/Thr protein kinase that is involved in various important biological processes. HIPK2 activates itself by auto-phosphorylation during its synthesis, and its activity is mainly controlled through modulation of its expression by ubiquitin-dependent degradation. By comparing the expression of wild-type and kinase-defective HIPK2, we have recently described a novel mechanism of HIPK2 regulation that is based on preferential co-translational degradation of kinase-defective versus wild-type HIPK2. Here, we have addressed this novel regulatory mechanism in more detail by focusing on the possible involvement of chaperones. Our work shows that HIPK2 is a client of the CDC37-HSP90 chaperone complex and points to a novel role of CDC37 in the co-translational degradation of a client protein.

Automated summary

HIPK2 is a constitutively active serine/threonine protein kinase involved in important biological processes, regulated by autophosphorylation during synthesis and ubiquitin-dependent degradation. A novel regulatory mechanism of HIPK2 involving preferential co-translational degradation of kinase-defective HIPK2 has been identified, with a potential role of chaperones such as CDC37-HSP90 complex in this process.