p73: A Multifunctional Protein in Neurobiology

被引：66

作者：

Killick, Richard

Niklison-Chirou, Maria ^{[1
]}

Tomasini, Richard ^{[2
]}

Bano, Daniele ^{[4
]}

Rufini, Alessandro ^{[1
]}

Grespi, Francesca ^{[1
]}

Velletri, Tania ^{[1
]}

Tucci, Paola ^{[1
]}

Sayan, Berna S. ^{[1
]}

Conforti, Franco ^{[1
]}

Gallagher, Ewen ^{[3
]}

Nicotera, Pierluigi ^{[4
]}

Mak, Tak W. ^{[5
]}

Melino, Gerry ^{[1
,6
,7
]}

Knight, Richard A. ^{[1
]}

Agostini, Massimiliano ^{[1
]}

机构：

[1] Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England

[2] INSERM, U624, F-13288 Marseille 9, France

[3] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London W12 0NN, England

[4] DZNE, D-53175 Bonn, Germany

[5] Princess Margaret Hosp, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada

[6] Univ Roma Tor Vergata, IDI IRCCS, Biochem Lab, I-00133 Rome, Italy

[7] European Brain Res Inst, Rome, Italy

来源：

MOLECULAR NEUROBIOLOGY | 2011年 / 43卷 / 02期

基金：

英国医学研究理事会;

关键词：

p73; Neuronal differentiation; Neural stem cells (NSC); Neurodegeneration; Alzheimer's Disease; GENOME-WIDE ASSOCIATION; AMYLOID-BETA-PEPTIDE; NEURAL STEM-CELLS; ALZHEIMERS-DISEASE; TERMINAL KINASE; C-ABL; NEURONAL DIFFERENTIATION; TAU PHOSPHORYLATION; IDENTIFIES VARIANTS; TUMOR-SUPPRESSOR;

D O I：

10.1007/s12035-011-8172-6

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

p73, a transcription factor of the p53 family, plays a key role in many biological processes including neuronal development. Indeed, mice deficient for both TAp73 and Delta Np73 isoforms display neuronal pathologies, including hydrocephalus and hippocampal dysgenesis, with defects in the CA1-CA3 pyramidal cell layers and the dentate gyrus. TAp73 expression increases in parallel with neuronal differentiation and its ectopic expression induces neurite outgrowth and expression of neuronal markers in neuroblastoma cell lines and neural stem cells, suggesting that it has a pro-differentiation role. In contrast, Delta Np73 shows a survival function in mature cortical neurons as selective Delta Np73 null mice have reduced cortical thickness. Recent evidence has also suggested that p73 isoforms are deregulated in neurodegenerative pathologies such as Alzheimer's disease, with abnormal tau phosphorylation. Thus, in addition to its increasingly accepted contribution to tumorigenesis, the p73 subfamily also plays a role in neuronal development and neurodegeneration.

引用

页码：139 / 146

页数：8

共 61 条

[1] p73 regulates maintenance of neural stem cell [J].