How Does p73 Cause Neuronal Defects?
The p53-family member, p73, plays a key role in the development of the central nervous system (CNS), in senescence, and in tumor formation. The role of p73 in neuronal differentiation is complex and involves several downstream pathways. Indeed, in the last few years, we have learnt that TAp73 directly or indirectly regulates several genes involved in neural biology. In particular, TAp73 is involved in the maintenance of neural stem/progenitor cell self-renewal and differentiation throughout the regulation of SOX-2, Hey-2, TRIM32 and Notch. In addition, TAp73 is also implicated in the regulation of the differentiation and function of postmitotic neurons by regulating the expression of p75NTR and GLS2 (glutamine metabolism). Further still, the regulation of miR-34a by TAp73 indicates that microRNAs can also participate in this multifunctional role of p73 in adult brain physiology. However, contradictory results still exist in the relationship between p73 and brain disorders, and this remains an important area for further investigation.
Toxicology Unit, Medical Research Council, Leicester, LE1 9HN, UK.|Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK.
Maria Victoria
MV
Niklison-Chirou
The Institute of Psychiatry, Psychology and Neuroscience, King's College London, Denmark Hill, London, SE5 8AF, UK.
Richard
R
Killick
Toxicology Unit, Medical Research Council, Leicester, LE1 9HN, UK.
Richard A
RA
Knight
DZNE, Ludwig-Erhard-Allee 2, 53175, Bonn, Germany.
Pierluigi
P
Nicotera
Toxicology Unit, Medical Research Council, Leicester, LE1 9HN, UK. gm89@le.ac.uk.|Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", 00133, Rome, Italy. gm89@le.ac.uk.
Gerry
G
Melino
Toxicology Unit, Medical Research Council, Leicester, LE1 9HN, UK. ma285@le.ac.uk.|Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", 00133, Rome, Italy. ma285@le.ac.uk.
Massimiliano
M
Agostini
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D006801:Humans; D008954:Models, Biological; D058953:Neural Stem Cells / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D000072160:Tumor Protein p73 / Q000378:metabolism*
D000072160:Tumor Protein p73
GLS2; Neurodegeneration; Neuronal differentiation; miR-34; p73, p75NTR