This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Chromosomal passenger (CP) proteins undergo dramatic changes in their distribution during the cell cycle, localizing to kinetochores, midzone, cleavage furrow and midbody at various stages of mitosis. CPs play critical roles in the proliferation and cell cycle checkpoint signaling pathways and are the subject of intense research due to their importance as mitotic regulators. Using an antibody (P190) generated against a phosphorylated peptide, we have observed 9 major proteins that are phosphorylated exclusively during mitosis where they behave as CPs. One of these proteins has been positively identified as Plk3 which is closely related to a known CP, Plk1. Plk1 has been extensively studied and is one of the key regulators of mitosis whose activity is controlled by transcriptional upregulation during G2 and proteasomal degradation at the completion of mitosis. Less is known about Plk3 function, but we hypothesize that it plays a similar role as Plk1 and is regulated by post-translational modifications during the cell cycle.
The aims of this project are: (1) Identify novel chromosomal passenger proteins using affinity pulldowns from HMEC cells; (2) Map phosphorylation sites on Plk3 and other CPs; and (3) Examine the composition of protein complexes containing specifically phosphorylated CPS as a function of the cell cycle, DNA damage, and oxidative stress.
Showing the most recent 10 out of 350 publications
