PP2AC alpha deficiency impairs early cortical development through inducing DNA damage in neuroprojenitor cells | |
Li, Rui4,5; Liu, Bo6,7; Deng, Chu-Xia2; Tong, Wei-Min2; Dong, Ting-Ting3,4; Lin, Lin4,7; Riazuddin, Saima6; Zubair, Ahmed6; Wang, Li1; Di, Li-Jun1 | |
刊名 | INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY |
2019-04-01 | |
卷号 | 109页码:40-58 |
关键词 | Protein phosphorylation Brain development DNA damage Stem cell Signaling cascade |
ISSN号 | 1357-2725 |
DOI | 10.1016/j.biocel.2019.01.021 |
通讯作者 | Liu, Bo(boliufhs@umac.mo) ; Deng, Chu-Xia(cxdeng@nih.gov) ; Tong, Wei-Min(wmtong@nih.gov) |
英文摘要 | The role of protein phosphatase 2AC alpha (PP2AC alpha) in brain development is poorly understood. To understand the function of PP2AC alpha in neurogenesis, we inactivated Pp2ac alpha gene in the central nervous system (CNS) of mice by Cre/LoxP system and generated the PP2AC alpha deficient mice (designated as the Pp2ac alpha(-/-) mice). PP2AC alpha deletion results in DNA damage in neuroprogenitor cells (NPCs), which impairs memory formation and cortical neurogenesis. We first identify that PP2AC alpha can directly associate with Ataxia telangiectasia mutant kinase (ATM) and Ataxia telangiectasia/Rad3-related kinase (ATR) in neocortex and NPCs. Importantly, the P53 and hypermethylated in cancer 1 (HIC1) function complex, the newly found down-stream executor of the ATR/ATM cascade, will be translocated into nuclei and interact with homeodomain interacting protein kinase 2 (HIPK2) to respond to DNA damage. Notably, HICI plays a direct transcriptional regulatory role in HIPK2 gene expression. The interplay among P53, HIC1 and HIPK2 maintains DNA stability in neuroprogenitor cells. Taken together, our findings highlight a new role of PP2AC alpha in regulating early neurogenesis through maintaining DNA stability in neuroprogenitor cells. The P53/HIC/HIPK2 regulation loop, directly targeted by the ATR/ATM cascade, is involved in DNA repair in neuroprogenitor cells. |
WOS关键词 | PROTEIN PHOSPHATASE 2A ; SERINE/THREONINE PHOSPHATASES ; MRE11 COMPLEX ; PP2A ; FAMILY ; DIFFERENTIATION ; ACTIVATION ; REPRESSORS ; SUBUNITS ; BREAKS |
WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
语种 | 英语 |
出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
WOS记录号 | WOS:000462103900006 |
内容类型 | 期刊论文 |
源URL | [http://cas-ir.dicp.ac.cn/handle/321008/165746] |
专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
通讯作者 | Liu, Bo; Deng, Chu-Xia; Tong, Wei-Min |
作者单位 | 1.Jones Hopkins Univ, Branch Canc Res, Baltimore, MD USA 2.NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA 3.China Agr Univ, Beijing, Peoples R China 4.Chinese Acad Sci, Inst Basic Med Sci, Dept Pathol, Beijing, Peoples R China 5.Chinese Acad Sci, Inst Biophys, Beijing, Peoples R China 6.Univ Maryland, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Baltimore, MD 21201 USA 7.Univ Macau, Macau, Peoples R China |
推荐引用方式 GB/T 7714 | Li, Rui,Liu, Bo,Deng, Chu-Xia,et al. PP2AC alpha deficiency impairs early cortical development through inducing DNA damage in neuroprojenitor cells[J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,2019,109:40-58. |
APA | Li, Rui.,Liu, Bo.,Deng, Chu-Xia.,Tong, Wei-Min.,Dong, Ting-Ting.,...&Di, Li-Jun.(2019).PP2AC alpha deficiency impairs early cortical development through inducing DNA damage in neuroprojenitor cells.INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,109,40-58. |
MLA | Li, Rui,et al."PP2AC alpha deficiency impairs early cortical development through inducing DNA damage in neuroprojenitor cells".INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY 109(2019):40-58. |
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