Anchoring of both PKA-RIIα and 14-3-3θ regulates retinoic acid induced 16 mediated phosphorylation of heat shock protein 70
| Autor: | Shi-Ying Zhu, Cui-Ling Ding, Wen Wang, Ping Zhao, Zhong-Tian Qi, Gang Xu, Hailin Tang, Lan-Juan Zhao, Hao Ren |
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| Rok vydání: | 2015 |
| Předmět: |
PKA-RIIα
Carcinoma Hepatocellular Immunoprecipitation Cell Survival Protein subunit Retinoic acid A Kinase Anchor Proteins Apoptosis Biology Cell Line Serine chemistry.chemical_compound AKAP Tandem Mass Spectrometry Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit Humans HSP70 Heat-Shock Proteins Phosphorylation Kinase Liver Neoplasms RAI16 Proteins Molecular biology 14-3-3θ Cell Transformation Neoplastic HEK293 Cells Oncology chemistry 14-3-3 Proteins Fam160B2 Signal transduction Signal Transduction Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Cui-Ling Ding 1,* , Gang Xu 1,* , Hai-Lin Tang 1 , Shi-Ying Zhu 1 , Lan-Juan Zhao 1 , Hao Ren 1 , Ping Zhao 1 , Zhong-Tian Qi 1 and Wen Wang 1 1 Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Zhong-Tian Qi, email: // Wen Wang, email: // Keywords : RAI16, Fam160B2, AKAP, PKA-RIIα, 14-3-3θ Received : January 19, 2015 Accepted : March 05, 2015 Published : March 30, 2015 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. |
| Databáze: | OpenAIRE |
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