title: Phosphorylation of caspase-8 (Thr-263) by ribosomal S6 kinase 2 (RSK2) mediates caspase-8 ubiquitination and stability.
abstract: The ribosomal S6 kinase 2 (RSK2) is a member of the p90 ribosomal S6 kinase (p90RSK) family of proteins and plays a critical role in proliferation, cell cycle, and cell transformation. Here, we report that RSK2 phosphorylates caspase-8, and Thr-263 was identified as a novel caspase-8 phosphorylation site. In addition, we showed that EGF induces caspase-8 ubiquitination and degradation through the proteasome pathway, and phosphorylation of Thr-263 is associated with caspase-8 stability. Finally, RSK2 blocks Fas-induced apoptosis through its phosphorylation of caspase-8. These data provide a direct link between RSK2 and caspase-8 and identify a novel molecular mechanism for caspase-8 modulation by RSK2.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
authors.forename: Cong
authors.initials: C
authors.lastname: Peng
authors.forename: Yong-Yeon
authors.initials: YY
authors.lastname: Cho
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Jishuai
authors.initials: J
authors.lastname: Zhang
authors.forename: Weihong
authors.initials: W
authors.lastname: Wen
authors.forename: Yanming
authors.initials: Y
authors.lastname: Xu
authors.forename: Ke
authors.initials: K
authors.lastname: Yao
authors.forename: Wei-Ya
authors.initials: WY
authors.lastname: Ma
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D053181:Caspase 8 / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D055550:Protein Stability; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013912:Threonine / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D013912:Threonine; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; C505530:CASP8 protein, human; D053181:Caspase 8