p62 modulates Akt activity via association with PKCzeta in neuronal survival and differentiation.
p62 is a ubiquitously expressed phosphoprotein that interacts with a number of signaling molecules and a major component of neurofibrillary tangles in the brain of Alzheimer's disease patients. It has been implicated in important cellular functions such as cell proliferation and anti-apoptotic pathways. In this study, we have addressed the potential role of p62 during neuronal differentiation and survival using HiB5, a rat neuronal progenitor cell. We generated a recombinant adenovirus encoding T7-epitope tagged p62 to reliably transfer p62 cDNA into the neuronal cells. The results show that an overexpression of p62 led not only to neuronal differentiation, but also to decreased cell death induced by serum withdrawal in HiB5 cells. In this process p62-dependent Akt phosphorylation occurred via the release of Akt from PKCzeta by association of p62 and PKCzeta, which is known as a negative regulator of Akt activation. These findings indicate that p62 facilitates cell survival through novel signaling cascades that result in Akt activation. Furthermore, we found that p62 expression was induced during neuronal differentiation. Taken together, the data suggest p62 is a regulator of neuronal cell survival and differentiation.
Joung
Insil
I
Department of Biology, Hanseo University, Seosan, Chungnam 352-820, Korea. ijoung@hanseo.ac.kr
Kim
Hak Jae
HJ
Kwon
Yunhee Kim
YK
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D000071456:Sequestosome-1 Protein; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*; D000099221:Protein Kinase C zeta
D048868:Adaptor Proteins, Signal Transducing; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000071456:Sequestosome-1 Protein; D000099221:Protein Kinase C zeta; C099718:SQSTM1 protein, human; C494918:AKT1 protein, human; C494920:Akt1 protein, rat