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

The cyclosome pathway of ubiquitin-mediated proteolysis plays 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 Fzy 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 G1, before the restriction point, and takes place also in G0. 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.