p73 can suppress the proliferation of cells that express mutant p53.
Mutation of the p53 tumor suppressor gene is the most common genetic alteration in human cancer. p73, a member of the p53 family, has been found to exhibit activity similar to that of p53, including the ability to induce growth arrest and apoptosis. p53 and p73 have a high percentage of similarity at several domains, including the DNA binding domain. This domain in p53 is the location of missense mutations in many human cancers. Mutant p53, which cannot suppress cell proliferation, has been found to have a dominant-negative activity that inactivates wild-type p53. To determine the effects of mutant p53 on wild-type p73, we have established cell lines expressing both mutant p53 and wild-type p73 in a dual-inducible system. This system expresses mutant p53 in a tetracycline-repressible system and p73beta in an ecdysone-inducible system in a p53-null lung carcinoma parental cell line. We have found that wild-type p73beta, in the presence of mutant p53, retains the ability to transactivate p21 and suppresses cell growth through induction of both cell cycle arrest and apoptosis. In addition, in cell lines expressing wild-type p53 and wild-type p73beta, we have found that these proteins cooperate to additively transactivate p21 and suppress cell proliferation.
Willis
Amy C
AC
Department of Cell Biology and UAB Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Pipes
Tara
T
Zhu
Jianhui
J
Chen
Xinbin
X
D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins