DICP OpenIR
PP2AC alpha deficiency impairs early cortical development through inducing DNA damage in neuroprojenitor cells
Liu, Bo1,2; Lin, Lin2,6; Riazuddin, Saima1; Zubair, Ahmed1; Wang, Li3; Di, Li-Jun3; Li, Rui5,6; Dong, Ting-Ting6,7; Deng, Chu-Xia4; Tong, Wei-Min4
Corresponding AuthorLiu, Bo(boliufhs@umac.mo) ; Deng, Chu-Xia(cxdeng@nih.gov) ; Tong, Wei-Min(wmtong@nih.gov)
KeywordProtein phosphorylation Brain development DNA damage Stem cell Signaling cascade
Source PublicationINTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
2019-04-01
ISSN1357-2725
DOI10.1016/j.biocel.2019.01.021
Volume109Pages:40-58
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS KeywordPROTEIN PHOSPHATASE 2A ; SERINE/THREONINE PHOSPHATASES ; MRE11 COMPLEX ; PP2A ; FAMILY ; DIFFERENTIATION ; ACTIVATION ; REPRESSORS ; SUBUNITS ; BREAKS
AbstractThe 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.
Language英语
WOS IDWOS:000462103900006
PublisherPERGAMON-ELSEVIER SCIENCE LTD
Citation statistics
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/165747
Collection中国科学院大连化学物理研究所
Corresponding AuthorLiu, Bo; Deng, Chu-Xia; Tong, Wei-Min
Affiliation1.Univ Maryland, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Baltimore, MD 21201 USA
2.Univ Macau, Macau, Peoples R China
3.Jones Hopkins Univ, Branch Canc Res, Baltimore, MD USA
4.NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA
5.Chinese Acad Sci, Inst Biophys, Beijing, Peoples R China
6.Chinese Acad Sci, Inst Basic Med Sci, Dept Pathol, Beijing, Peoples R China
7.China Agr Univ, Beijing, Peoples R China
Recommended Citation
GB/T 7714
Liu, Bo,Lin, Lin,Riazuddin, Saima,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 Liu, Bo.,Lin, Lin.,Riazuddin, Saima.,Zubair, Ahmed.,Wang, Li.,...&Tong, Wei-Min.(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 Liu, Bo,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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