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.
Department of Histology Microbiology and Medical iotechnologies, Section of Histology and Embryology, University of Padua, viale Colombo 3, 35121, Italy.
Sirio
S
Dupont
Luca
L
Zacchigna
Maddalena
M
Adorno
Sandra
S
Soligo
Dino
D
Volpin
Stefano
S
Piccolo
Michelangelo
M
Cordenonsi
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