This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human cyclin K is a member of the transcription cyclin family and plays an important role in regulating basal transcription through its association with and activation of the cyclin-dependent kinase 9 (CDK9). The CDK9-cyclin K complex phosphorylates the C-terminal domain of the large subunit of RNA polymerase II and regulates the transcriptional elongation step. Positive transcription elongation factor b (P-TEFb) complexes isolated from mammalian cells contain the common catalytic subunit CDK9 and the unique regulatory cyclins K, T1 or T2. CDK9-Cyclin K functions as P-TEFb only via RNA suggesting the presence of cellular RNA-bound activators that require cyclin K for their transcriptional activity. Furthermore, cyclin K is a direct transcription target of the tumor suppressor p53 and has an important function in regulation of the cell cycle or apoptosis. We determined the crystal structure of human cyclin K at 1.8 resolution using multiple isomorphous replacement. Since the crystals diffract to higher resolution, we wish to improve the present structure by collecting high resolution data at X29. Cryo-conditions have been established and we currently have a large number of frozen crystals ready for data collection. Because the human cyclin K is closely related to human cyclin T1 that binds to the HIV-1 transactivator Tat and TAR RNA, the crystal structure of cyclin K will be useful for modeling the cyclin T1 and its interaction with Tat.
Showing the most recent 10 out of 167 publications
