p53 Brings a New Twist to the Smad Signaling Network

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.