title: Anchoring of both PKA-RIIα and 14-3-3θ regulates retinoic acid induced 16 mediated phosphorylation of heat shock protein 70.
abstract: Our previous study reported that retinoic acid induced 16 (RAI16) could enhance tumorigenesis in hepatocellular carcinoma (HCC). However, the cellular functions of RAI16 are still unclear. In this study, by immunoprecipitation and tandem (MS/MS) mass spectrometry analysis, we identified that RAI16 interacted with the type II regulatory subunit of PKA (PKA-RIIα), acting as a novel protein kinase A anchoring protein (AKAP). In addition, RAI16 also interacted with heat shock protein 70 (HSP70) and 14-3-3θ. Further studies indicated that RAI16 mediated PKA phosphorylation of HSP70 at serine 486, resulting in anti-apoptosis events. RAI16 was also phosphorylated by the anchored PKA at serine 325, which promoted the recruitment of 14-3-3θ, which, in turn, inhibited RAI16 mediated PKA phosphorylation of HSP70. These findings offer mechanism insight into RAI16 mediated anti-apoptosis signaling in HCC.
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China.
authors.forename: Cui-Ling
authors.initials: CL
authors.lastname: Ding
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China.
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Tang
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Zhu
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China.
authors.forename: Lan-Juan
authors.initials: LJ
authors.lastname: Zhao
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China.
authors.forename: Zhong-Tian
authors.initials: ZT
authors.lastname: Qi
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit / Q000378:metabolism*; D057809:HEK293 Cells; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry
chemical_list: D048948:14-3-3 Proteins; D054758:A Kinase Anchor Proteins; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit; D018840:HSP70 Heat-Shock Proteins; D011506:Proteins; C547416:FHIP2B protein, human; C517819:PRKAR2A protein, human
keywords: 14-3-3θ; AKAP; Fam160B2; PKA-RIIα; RAI16