Cyclin A recruits p33(cdk2) to the cellular transcription factor DRTF1
Bandara LR., Adamczewski JP., Zamanian M., Poon RYC., Hunt T., La Thangue NB.
Cyclins are regulatory molecules that undergo periodic accumulation and destruction during each cell cycle. By activating p34(cdc2) and related kinase subunits they control important events required for normal cell cycle progression. Cyclin A, for example, regulates at least two distinct kinase subunits, the mitotic kinase subunit p34(cdc2) and related subunit p33(cdk2), and is widely believed to be necessary for progression through S phase. However, cyclin A also forms a stable complex with the cellular transcription factor DRTF1 and thus may perform other functions during S phase. DRTF1, in addition, associates with the tumour suppressor retinoblastoma (Rb) gene product and the Rb-related protein p107. We now show, using biologically active fusion proteins, that cyclin A can direct the binding of the cdc2-like kinase subunit, p33(cdk2), to complexed DRTFl, containing either Rb or p107, as well as activate its histone H1 kinase activity. Cyclin A cannot, however, direct p34(cdc2) to the DRTF1 complex and we present evidence suggesting that the stability of the cyclin A-p33(cdk2) complex is influenced by DRTF1 or an associated protein. Cyclin A, therefore, serves as an activating and targeting subunit of p33(cdk2). The ability of cyclin A to activate and recruit p33(cdk2) to DRTF1 may play an important role in regulating cell cycle progression and moreover defines a mechanism for coupling cell-cycle events to transcriptional initiation.