Dysfunction of apoptotic pathways plays a critical role in the development of cancer, and the identification and characterization of genes encoding regulators of apoptosis is therefore critical for understanding the pathophysiology of cancer and for developing novel therapeutic approaches. The laboratory has identified CIPER, a gene that regulates both apoptosis and the NF-kB signal transduction pathway, one which is associated with cell survival. Because of this dual function, CIPER appears to play an important role as the control point of a molecular decision-tree; under some circumstances, CIPER may promote apoptosis, while at other times CIPER may favor cell survival. Importantly, the CIPER gene has been found to be located at the chromosomal breakpoint region of t(1;14), a recurrent translocation associated with MALT B-cell lymphoma, and is frequently mutated in lymphomas of various other histologic types as well as some non-lymphoid neoplasms. Our hypothesis is that CIPER promotes tumor development through a combination of dysregulated apoptosis and NF-kB signaling which result from chromosomal mutations affecting the CIPER gene. We are proposing a series of aims to further define the molecular mechanisms by which CIPER controls these signaling pathways, to understand the cellular stimulae which influence CIPER function, and to explore how natural mutations in the CIPER gene affect its important role as a regulator of cell survival.
| Muto, Akihiro; Ruland, Jurgen; McAllister-Lucas, Linda M et al. (2002) Protein kinase C-associated kinase (PKK) mediates Bcl10-independent NF-kappa B activation induced by phorbol ester. J Biol Chem 277:31871-6 |
| Lucas, P C; Yonezumi, M; Inohara, N et al. (2001) Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway. J Biol Chem 276:19012-9 |
| McAllister-Lucas, L M; Inohara, N; Lucas, P C et al. (2001) Bimp1, a MAGUK family member linking protein kinase C activation to Bcl10-mediated NF-kappaB induction. J Biol Chem 276:30589-97 |
