p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition.
It has been reported that prostate apoptosis response-4 (PAR-4) binds to and inhibits protein kinase Czeta (PKCzeta) which phosphorylates IkappaB kinase beta (IKKbeta) for nuclear factor kappaB (NFkappaB) activation, while p62 binds to and recruits PKCzeta to the NFkappaB signaling complex. Thus, a mechanism to coordinate the two binding proteins for the regulation of PKCzeta is expected to exist. The present data show that p62 and PAR-4 do not compete for PKCzeta binding but directly interact each other and form a ternary complex with PKCzeta. Furthermore, p62 not only enhances the catalytic activity of PKCzeta but also reactivates catalytically inactive PAR-4-bound PKCzeta. As the result, over-expression of p62 protects cells from PAR-4-mediated inactivation of NFkappaB and apoptotic death. Thus, the regulatory role of p62 for free and PAR-4-bound PKCzeta is important in activation of NFkappaB.
Chang
Suhwan
S
School of Medicine, Sunkyunkwan University, 300 ChunChun-Dong, Jangan-Gu, Suwon, Kyonggi-Do, South Korea.
Kim
Jung Hoe
JH
Shin
Jaekyoon
J
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000099221:Protein Kinase C zeta
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D016328:NF-kappa B; D011493:Protein Kinase C; D011993:Recombinant Fusion Proteins; D000099221:Protein Kinase C zeta; C101296:prostate apoptosis response-4 protein