title: HDAC4 protects cells from ER stress induced apoptosis through interaction with ATF4.
abstract: Histone deacetylase 4 (HDAC4) is involved in the regulation of many fundamental cell processes such as proliferation, differentiation, and survival via the modification of their substrates or protein-protein interactions. In this study, we found that HDAC4 could be upregulated under ER stress. There exists a direct interaction between HDAC4 and activating transcription factor 4 (ATF4). In vitro, overexpression of HDAC4 caused the retention of ATF4 in cytoplasm and inhibition of ATF4 transcriptional activity. ER stress could promote cell apoptosis through the upregulation of ATF4 levels and its target genes such as CHOP and TRB3. This effect was exacerbated by downregulation of HDAC4 levels. These results demonstrated that HDAC4 played an important role in the regulation of ER stress-induced apoptosis through interacting with ATF4 and inhibiting its transcriptional activity.
authors.affiliation: Key Lab of Physiology, Biochemistry & Molecular Biology of Hebei Province, Hebei Normal University, Shijiazhuang 050024, China; State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Key Lab of Physiology, Biochemistry & Molecular Biology of Hebei Province, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China.
authors.forename: Shukuan
authors.initials: S
authors.lastname: Ling
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Key Lab of Physiology, Biochemistry & Molecular Biology of Hebei Province, Hebei Normal University, Shijiazhuang 050024, China. Electronic address: chang7676@163.com.
authors.forename: Yan-Zhong
authors.initials: YZ
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China. Electronic address: yingxianli@aliyun.com.
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Li
mesh_terms: D016475:3T3 Cells; D051701:Activating Transcription Factor 4 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D057809:HEK293 Cells; D006655:Histone Deacetylases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation; D019892:eIF-2 Kinase / Q000096:biosynthesis / Q000378:metabolism
chemical_list: C497109:ATF4 protein, human; D018797:Cell Cycle Proteins; C497249:DDIT3 protein, human; D004791:Enzyme Inhibitors; D015852:Eukaryotic Initiation Factor-2; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C474831:TRIB3 protein, human; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP; D019284:Thapsigargin; C460640:EIF2AK3 protein, human; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; C400300:HDAC4 protein, human; D006655:Histone Deacetylases; D000252:Calcium-Transporting ATPases
keywords: ATF4; Cell apoptosis; Endoplasmic reticulum stress; HDAC4