p53 Brings a New Twist to the Smad Signaling Network
Azeddine Atfi1,2* and
Roland Baron2
1INSERM U893, Hôpital St-Antoine, 184 Rue du Faubourg St-Antoine, 75571 Paris, France.
2Harvard School of Dental Medicine, Department of Oral Medicine, Infection and Immunity; and Harvard Medical School and Internal Medicine, Endocrine Unit, Massachusetts General Hospital, 188 Longwood Avenue, Boston, MA 02115, USA.
Abstract:
Transforming growth factor beta (TGF-β) signaling regulates a plethora of cellular responses, including specification of developmental fate during embryogenesis, cell proliferation, differentiation, and apoptosis. Components of this pathway are often mutated in cancers and other human disorders. TGF-β signaling involves activation of transcriptional regulators of the Smad family. The tumor suppressor p53 is an essential partner of Smads, affecting TGF-β signaling at various points in the pathway. Inactivation of p53 may contribute to the aberrant behavior of cancer cells that escape the cytostatic action of TGF-β despite the apparent integrity of the TGF-β receptor or Smads. Thus, the discovery that p53 and TGF-β cooperate in cell-fate decisions and cellular homeostatic mechanisms has important pathophysiological implications.
*Corresponding author. E-mail: azeddine.atfi{at}inserm.fr
