title: The role of lipid raft translocation of prohibitin in regulation of Akt and Raf-protected apoptosis of HaCaT cells upon ultraviolet B irradiation.
abstract: Prohibitin (PHB) plays a role in regulation of ultraviolet B light (UVB)-induced apoptosis of human keratinocytes, HaCaT cells. The regulatory function of PHB appears to be associated with its lipid raft translocation. However, the detailed mechanism for PHB-mediated apoptosis of these keratinocytes upon UVB irradiation is not clear. In this report, we determined the role of lipid raft translocation of PHB in regulation of UVB-induced apoptosis. Our data show that upon UVB irradiation PHB is translocated from the non-raft membrane to the lipid rafts, which is correlated with a release of both Akt and Raf from membrane. Overexpression of Akt and/or Raf impedes UVB-induced lipid raft translocation of PHB. Immunoprecipitation analysis indicates that UVB alters the interactions among PHB, Akt, and Raf. Reduced expression of PHB leads to a decreased phosphorylation of Akt and ERK, as well as a decreased activity of Akt, and increased apoptosis of the cells upon UVB irradiation. These results suggest that PHB regulates UVB-induced apoptosis of keratinocytes via a mechanism that involves detachment from Akt and Raf on the plasma membrane, and sequential lipid raft translocation.
authors.affiliation: Department of Chemistry and Biochemistry, Edison Biotechnology Institute, Ohio University, Athens, Ohio.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Chemistry and Biochemistry, Edison Biotechnology Institute, Ohio University, Athens, Ohio.
authors.forename: Shiyong
authors.identifier: 0000-0002-4104-4160
authors.initials: S
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D021962:Membrane Microdomains / Q000378:metabolism* / Q000528:radiation effects; D010766:Phosphorylation; D000091402:Prohibitins; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014466:Ultraviolet Rays; D048490:raf Kinases / Q000378:metabolism*
chemical_list: C000717328:PHB protein, human; D000091402:Prohibitins; D012097:Repressor Proteins; D051057:Proto-Oncogene Proteins c-akt; D048490:raf Kinases
keywords: apoptosis; lipid raft; prohibitin; ultraviolet B light