): The investigator is a clinical pathologist in early academic practice at Northwestern University Medical School with primary research interest in the molecular biology of the oncoprotein Bcl-2. This institution has demonstrated an exceptional commitment to develop a strong multidisciplinary program in cancer research by establishing the Robert H. Lurie Cancer Center that unites 236 basic and clinical researchers. The investigator has been recruited to develop an independent basic research laboratory focusing on the role of the Bcl-2 oncoprotein in tumorigenesis. A summary of the applicant's research plan follows. Apoptosis, or programmed cell death, is an active form of cellular suicide that functions in a variety of physiological and developmental systems to ensure that superfluous or unwanted cells are eliminated. This process is also of great significance in the treatment of cancer, as most chemotherapeutic agents function by inducing apoptosis. The oncoprotein, Bcl-2 can block or delay apoptosis in many instances, and when expressed in malignant cells often renders chemotherapy ineffective. Bcl-2 can also slow cell cycle progression, but it is not known if this effect is related to Bcl-2's apoptosis countering function. The investigators have now observed, that Bcl-2 can delay cell cycle progression independently of its effect on apoptosis, and that this property of Bcl-2 may be dependent on its phosphorylation status. Based on their preliminary data they hypothesize that the physiologic (antiapoptotic and antiproliferative) vs. pro-oncogenic (only antiapoptotic) mechanism of Bcl-2 is determined and regulated by its phosphorylation. In this grant proposal they wish to examine the mechanism by which Bcl-2 delay cell cycle progression, the role of phosphorylated Bcl-2 in cell cycle and apoptosis regulation, and identify and characterize the Bcl-2 kinase protein.
| Poommipanit, P B; Chen, B; Oltvai, Z N (1999) Interleukin-3 induces the phosphorylation of a distinct fraction of bcl-2. J Biol Chem 274:1033-9 |
| St Clair, E G; Anderson, S J; Oltvai, Z N (1997) Bcl-2 counters apoptosis by Bax heterodimerization-dependent and -independent mechanisms in the T-cell lineage. J Biol Chem 272:29347-55 |
