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

Abstract

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 p73gamma and epsilon. Sequence analysis revealed that these mRNAs encode variant p73 proteins bearing distinct carboxy-terminal structures, which are also different from the previously reported variants p73alpha and beta. The mRNAs encoding p73gamma 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 activated promoter with the p53-binding consensus sequence, but to different degrees. Furthermore, suppressive effects of p73alpha, gamma and epsilon, but not beta, on endogenous p53 activity were observed when transiently expressed in HepG2 and MCF-7 cells. These results suggested that the carboxy-terminal regions of p73 which were altered by alternative splicing affect these transactivation abilities and modulate the functions of p73 molecules.