New p73 variants with altered C-terminal structures have varied transcriptional activities

p73 has been identified as a protein which shares significant homology with the tumor suppressor p53, We found two new types of splicing variant mRNAs for p73 expressed in MCF-7 cells which we named p73 gamma and epsilon. Seq uence analysis revealed that these mRNAs encode variant p73 proteins bearin g distinct carboxy-terminal structures, which are also different from the p reviously reported variants p73 alpha and beta, The mRNAs encoding p73 gamm a and epsilon as well as alpha. and beta were confirmed to be expressed in normal human tissues in varied patterns. All of these splicing variants act ivated promoter with the p53-binding consensus sequence, but to different d egrees. Furthermore, suppressive effects of p73 alpha, gamma and epsilon, b ut not beta, on endogenous p53 activity were observed when transiently expr essed in HepG2 and MCF-7 cells. These results suggested that the carboxy-te rminal regions of p73 which were altered by alternative splicing affect the se transactivation abilities and modulate the functions of p73 molecules.