Lonely No More: p53 Finds Its Kin in a Tumor Suppressor Haven

摘要: The discovery of p73 sheds new light on a number well-known facts about p53. One the most obvious is almost normal development p53 knock-out mice (Donehower et al. 1992xDonehower, L.A., Harvey, M., Slagle, B.L., MacArthur, M.J., Montgomery, C.A. Jr., Butel, J.S., and Bradly, A. Nature. 1992; 356: 215–221Crossref | PubMed Scopus (2761)See all ReferencesDonehower 1992). Given numerous reports role in differentiation, apoptosis, proliferation cultured cells, lack dramatic developmental phenotypes was rather disappointing. Although some defects were later uncovered, they limited scope penetrance. With other key regulatory proteins, mild single knock-outs explained by functional redundancy with family members. However, such explanation could not be offered for Not until p73, that is. It may now proposed doubles up p53, only fails to do so under conditions genomic damage, where specific function becomes irreplaceable. Of note, main difference far between latter protein neither stabilized nor activated DNA damage (Kaghad 1997xKaghad, Bonnet, H., Yang, A., Creancier, L., Biscan, J.-C., Valent, Minty, Chalon, P., Lelias, J.-M., Dumont, X. Cell. 1997; 90: 809–819Abstract Full Text PDF (1365)See ReferencesKaghad see Figure 2Figure 2). Hence, it play monitoring damage. As possibility substitutes functions answer likely come from crosses knock-outs. On cautionary has been identified, there no compelling reason exclude existence additional Such yet-to-be-uncovered genes are complicate genetic analysis.Another observation explain that, unlike tumors, neuroblastomas very rarely carry mutations (Ohgaki 1993xOhgaki, Eibl, R.H., Schwab, Reichel, M.B., Mariani, Gehring, Petersen, I., Holl, T., Wiestler, O.D., Kleihues, P. Mol. Carcinog. 1993; 8: 74–80Crossref PubMedSee ReferencesOhgaki 1993). particular cells give rise neuroblastoma than performs crucial tumor suppressor job. once inactivated, will significant selective pressure inactivate as well. actual picture is, however, more complex. While gene remains wild-type neuroblastomas, misplaced: being nuclear, accumulates cytoplasm (Ostermeyer 1996xOstermeyer, A.G., Runko, E., Winkfield, B., Ahn, Moll, U.M. Proc. Natl. Acad. Sci. USA. 1996; 93: 15190–15194Crossref (96)See ReferencesOstermeyer 1996). presently controversial whether this truly inactivation which blocks its ability respond stress maintain integrity. Yet, if cytoplasmic sequestration results incapacitation, make need invoke less obvious. Even so, one still propose underlies retention Future work should clarify issue.It thus yet proven long sought-after 1p gene. In particular, worries inability find coding region cell lines tested date. This concern strengthened knowledge point mutations, analogous those observed human cancer, indeed suffice abrogate antiproliferative effect 1997). high frequency puzzling same does pertain (Table 1Table 1). imprinted nature locus offers reasonable explanation, equally possible just happens reside within chromosomal harboring cluster genes, real actually p73's neighbors. To resolve important issue, either eventually necessarily neuroblastoma, bear inactivating or else go systematically through entire 8 Mb rule out neighboring one.In relatively short history, research already seen surprising twists. another major turning along road. Judging past experience, quite safe predict soon become latest spin-off develop into “hot” topic own right.