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 p73γ and ε. Sequence analysis revealed that these mRNAs encode variant p73 proteins bearing distinct carboxy-terminal structures, which are also different from the previously reported variants p73α and β. The mRNAs encoding p73γ and ε as well as α and β 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 p73α, γ and ε, but not β, 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.