Convergence of p53 and TGF-beta signaling networks.
p53 is a protein with many talents. One of the most fundamental is the ability to act as essential growth checkpoint that protects cells against cellular transformation. p53 does so through the induction of genes leading to growth arrest or apoptosis. Most of the studies focusing on the mechanisms of p53 activity have been performed in cultured cells upon treatment with well-established p53-activating inputs, such as high doses of radiations, DNA-damaging drugs and activated oncogenes. However, how the tumor suppressive functions of p53 become concerted with the extracellular cues arriving at the cell surface during tissue homeostasis, remains largely unknown. Intriguingly, two recent papers have shed new light into this unexplored field, indicating that p53 plays a key role in TGF-beta-induced growth arrest and, unexpectedly, in the developmental effects of TGF-beta in early embryos. Here we review and comment on these findings and on their implications for cancer biology.
Dupont
Sirio
S
Department of Histology Microbiology and Medical iotechnologies, Section of Histology and Embryology, University of Padua, viale Colombo 3, 35121, Italy.
Zacchigna
Luca
L
Adorno
Maddalena
M
Soligo
Sandra
S
Volpin
Dino
D
Piccolo
Stefano
S
Cordenonsi
Michelangelo
M
D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004249:DNA Damage; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D006128:Growth / Q000235:genetics; D006706:Homeostasis; D006801:Humans; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53