p53 and TGF-β in Development Prelude to Tumor Suppression?

interacts with the C-terminal MH2 domain, raising the possibility (not investigated here) that Smad2 bridges two different site specific DNA binding factors to generate a more complex, and potentially more specific, Recent work in Xenopus embryos reveals an unex-multifactor DNA binding complex. p53 facilitates activin-pected developmental role for the tumor suppressor regulated but not BMP-regulated signals in the Xenopus gene p53. This finding may have implications for the embryo, and regulates only a subset of early transcrip-evolution of p53, its interaction with Smads in TGF-␤ tional responses to activin—supporting the idea that dependent mesoderm specification, and the coopera-p53 is targeting Smad2/3 to specific activin responsive tion among p53 family members. promoters. p53 thus appears to fit nicely into a novel role as a DNA binding cofactor for Smad signaling, and in early Xenopus embryos is important for normal ex-The remarkable finding of mice lacking p53 was not that pression of a subset of mesendodermal genes. they develop tumors, but rather that they existed at Also undefined is p53's relationship to patterning in all. Given the vaunted attributes of the p53 protein in the embryo. While morpholino antisense inhibition of monitoring cellular proliferation and homeostasis, as p53 expression demonstrates a necessary role for p53 well as effecting cell death and premature senescence, in axial patterning of the Xenopus embryo, whether p53 the absence of developmental defects in the p53 null activity is itself patterned during embryogenesis is a mice came as a surprise. Despite the starkness of this central unanswered question in understanding the em-result, subsequent findings have been nagging remind-bryological role of p53. In Xenopus, p53 protein is ex-ers of the expected developmental role of p53: the early pressed at high levels maternally, and does not appear embryonic death of mice deficient for the p53 regulator to be obviously localized during the period when Mix.2 Mdm2, apparent interactions between p53 and TGF-␤ is expressed and axial pattern is initially established in proliferation checkpoints, and the newly discovered (Tchang et al., 1993). Numerous posttranslational mech-family of p53 homologs having obvious developmental anisms for p53 regulation have been identified or proposed , however, leaving open the possibility that p53 et al., 2002). The present paper by Piccolo and col-activity, rather than p53 protein per se, is localized to leagues (Cordenonsi et al., 2003) presents intriguing regulate specific patterns of TGF-␤-responsive gene ex-data in support of cooperation between p53 and TGF-␤ pression in …