The mammalian Fizzy and Fizzy-related genes are regulated at the transcriptional and post-transcriptional levels

The cyclosome pathway of ubiquitin-mediated proteolysis pla;vs an essential role in cell cycle control, The multisubunit cyclosome is regulated by transient interactions with Fizzy (Fzy) and Fizzy-related (Fzr) genes, We report here that both Fz?; and Fzr are transcribed in a cell cycle specific but distinct manner, Fzy transcription starts after the restriction point in late G1 and ceases upon cell division. Fzr transcription also ceases upon cell division but resumes already in mid GI, before the restriction point, and takes place also in GO. Fzr has further a striking cell cycle specific pattern of mRNA stability, During most of the cell cycle its message is fairly stable, however upon exit from mitosis it is rapidly degraded. This result is puzzling because Fzr is essential for cyclosome activity in G1, and points to a complex pattern of Fzr regulation, (C) 1999 Federation of European Biochemical Societies.