TY - JOUR
T1 - A glance of p53 functions in brain development, neural stem cells, and brain cancer
AU - Xiong, Yuqing
AU - Zhang, Yun
AU - Xiong, Shunbin
AU - Williams-Villalobo, Abie E.
N1 - Funding Information:
Funding: Y.X. was funded by NIA grant T35AG044303. Y.Z. has been funded by NIH RCMI grant 5G12MD007605-23, CPRIT grant RP180748 and NIGMS grant 1SC2GM135111-01.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/9
Y1 - 2020/9
N2 - p53 is one of the most intensively studied tumor suppressors. It transcriptionally regulates a broad range of genes to modulate a series of cellular events, including DNA damage repair, cell cycle arrest, senescence, apoptosis, ferroptosis, autophagy, and metabolic remodeling, which are fundamental for both development and cancer. This review discusses the role of p53 in brain development, neural stem cell regulation and the mechanisms of inactivating p53 in gliomas. p53 null or p53 mutant mice show female biased exencephaly, potentially due to X chromosome inactivation failure and/or hormone-related gene expression. Oxidative cellular status, increased PI3K/Akt signaling, elevated ID1, and metabolism are all implicated in p53-loss induced neurogenesis. However, p53 has also been shown to promote neuronal differentiation. In addition, p53 mutations are frequently identified in brain tumors, especially glioblastomas. Mechanisms underlying p53 inactivation in brain tumor cells include disruption of p53 protein stability, gene expression and transactivation potential as well as p53 gene loss or mutation. Loss of p53 function and gain-of-function of mutant p53 are both implicated in brain development and tumor genesis. Further understanding of the role of p53 in the brain may provide therapeutic insights for brain developmental syndromes and cancer.
AB - p53 is one of the most intensively studied tumor suppressors. It transcriptionally regulates a broad range of genes to modulate a series of cellular events, including DNA damage repair, cell cycle arrest, senescence, apoptosis, ferroptosis, autophagy, and metabolic remodeling, which are fundamental for both development and cancer. This review discusses the role of p53 in brain development, neural stem cell regulation and the mechanisms of inactivating p53 in gliomas. p53 null or p53 mutant mice show female biased exencephaly, potentially due to X chromosome inactivation failure and/or hormone-related gene expression. Oxidative cellular status, increased PI3K/Akt signaling, elevated ID1, and metabolism are all implicated in p53-loss induced neurogenesis. However, p53 has also been shown to promote neuronal differentiation. In addition, p53 mutations are frequently identified in brain tumors, especially glioblastomas. Mechanisms underlying p53 inactivation in brain tumor cells include disruption of p53 protein stability, gene expression and transactivation potential as well as p53 gene loss or mutation. Loss of p53 function and gain-of-function of mutant p53 are both implicated in brain development and tumor genesis. Further understanding of the role of p53 in the brain may provide therapeutic insights for brain developmental syndromes and cancer.
KW - Brain
KW - Development
KW - Gain-of-function
KW - Glioma
KW - Mutation
KW - Neural stem cell
KW - P53
UR - http://www.scopus.com/inward/record.url?scp=85090839037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85090839037&partnerID=8YFLogxK
U2 - 10.3390/biology9090285
DO - 10.3390/biology9090285
M3 - Review article
C2 - 32932978
AN - SCOPUS:85090839037
SN - 2079-7737
VL - 9
SP - 1
EP - 13
JO - Biology
JF - Biology
IS - 9
M1 - 285
ER -