PHLDA3 impedes somatic cell reprogramming by activating Akt-GSK3β pathway

Mengran Qiao; Mian Wu; Ronghua Shi; Wanglai Hu

doi:10.1038/s41598-017-02982-9

PHLDA3 impedes somatic cell reprogramming by activating Akt-GSK3β pathway

Sci Rep. 2017 Jun 6;7(1):2832. doi: 10.1038/s41598-017-02982-9.

Authors

Mengran Qiao¹, Mian Wu², Ronghua Shi³, Wanglai Hu⁴

Affiliations

¹ CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Cell and Molecular Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science & Technology of China, Hefei, 230027, China.
² CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Cell and Molecular Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science & Technology of China, Hefei, 230027, China. wumian@ustc.edu.cn.
³ CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Cell and Molecular Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science & Technology of China, Hefei, 230027, China. rhsh@ustc.edu.cn.
⁴ Department of Immunology, Anhui Medical University, Hefei, 230032, China. wanglaihu@ahmu.edu.cn.

Abstract

Reprogramming of adult somatic cells into induced pluripotent stem cells holds great promise in clinical therapy. Increasing evidences have shown that p53 and its target genes play important roles in somatic cell reprogramming. In this study, we report that PHLDA3, a p53 target gene, functions as a blockage of iPSCs generation by activating the Akt-GSK3β pathway. Furthermore, PHLDA3 is found to be transcriptionally regulated by Oct4. These findings reveal that PHLDA3 acts as a new member of the regulatory network of somatic cell reprogramming.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cellular Reprogramming*
Gene Expression
Gene Expression Regulation, Developmental
Glycogen Synthase Kinase 3 beta / metabolism*
Humans
Induced Pluripotent Stem Cells / metabolism
Mice
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Octamer Transcription Factor-3 / metabolism
Proto-Oncogene Proteins c-akt / metabolism*
Transcription, Genetic

Substances

Nuclear Proteins
Octamer Transcription Factor-3
TSSC3 protein
Glycogen Synthase Kinase 3 beta
Proto-Oncogene Proteins c-akt