title: Sox2 protects neural stem cells from apoptosis via up-regulating survivin expression.
abstract: The transcription factor Sox2 [SRY (sex-determining region Y)-box 2] is essential for the regulation of self-renewal and homoeostasis of NSCs (neural stem cells) during brain development. However, the downstream targets of Sox2 and its underlying molecular mechanism are largely unknown. In the present study, we found that Sox2 directly up-regulates the expression of survivin, which inhibits the mitochondria-dependent apoptotic pathway in NSCs. Although overexpression of Sox2 elevates survivin expression, knockdown of Sox2 results in a decrease in survivin expression, thereby initiating the mitochondria-dependent apoptosis related to caspase 9 activation. Furthermore, cell apoptosis owing to knockdown of Sox2 can be rescued by ectopically expressing survivin in NSCs as well as in the mouse brain, as demonstrated by an in utero-injection approach. In short, we have found a novel Sox2/survivin pathway that regulates NSC survival and homoeostasis, thus revealing a new mechanism of brain development, neurological degeneration and such aging-related disorders.
authors.affiliation: Peking University Stem Cell Research Center and Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China, 100191.
authors.forename: Ruopeng
authors.initials: R
authors.lastname: Feng
authors.forename: Shixin
authors.initials: S
authors.lastname: Zhou
authors.forename: Yinan
authors.initials: Y
authors.lastname: Liu
authors.forename: Daijun
authors.initials: D
authors.lastname: Song
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Luan
authors.forename: Xin
authors.initials: X
authors.lastname: Dai
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Tang
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wen
authors.forename: Lingsong
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000077022:Survivin; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D000077022:Survivin