CYCLIN-E-T, A NEW SPLICE VARIANT OF HUMAN CYCLIN-E WITH A UNIQUE EXPRESSION PATTERN DURING CELL-CYCLE PROGRESSION AND DIFFERENTIATION

Cyclin E is the regulatory subunit of the cdc2-related protein kinase cdk2 and is a rate limiting factor for the entry into S phase. To date , cyclin E is the only cyclin for which alternative splicing has been described. We report here the isolation of a new splice variant of cyc lin E, termed cyclin E-T, which has an internal deletion of 45 amino a cids compared with the full-length cyclin E protein. Even though cycli n E-T contains an intact cyclin box, it is unable to complement a trip le cln mutant strain of Saccharomyces cerevisiae or to interfere with rescue by cyclin E, indicating that an intact cyclin box is functional ly insufficient. The expression pattern of cyclin E-T during cell cycl e entry, progression and differentiation differs from that of cyclin E . Thus, E-T expression precedes that of the other isoforms during the G(0) --> S progression; it shows a sharp peak in early G(1) in cells r eleased from a mitotic block and is strongly down-regulated in termina lly differentiated myeloid cells. These observations point to differen t functions for cyclin E-T and E and show for the first time that the alternative splicing of cyclin E is a regulated mechanism governed by the cell cycle and differentiation.