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Function of Protein Kinase PKK in B-cell Malignancies

Project Overview

B-cell lymphomas are the fifth common cancer type in United States and affect nearly half a million Americans. Despite recent advances in treatment, a significant proportion of patients still die from B-cell lymphomas (approximately 20,000 people will die from the disease each year in U.S. as estimated by Lymphoma Research Foundation). Thus, new treatment strategies are needed to combat this deadly disease.

We have shown that the PKCb-associated kinase PKK is crucial for NF-kB activation in human diffuse large B cell lymphoma (DLBCL) cells. In addition, we have found that protein kinase PKK is required for NF-kB activation by BAFF (B cell activation factor belonging to the TNF family) signaling, which is emerging as a contributing factor for tumorigenesis of B-lymphocytes. Importantly, we have demonstrated that suppression of PKK expression impairs the proliferation/survival of human diffuse large B cell lymphoma (DLBCL) cells in vitro, and reduces tumor growth of xenografted DLBCL cells in NOD/SCID mice. These results suggest that PKK represents a potential therapeutic target for certain B-cell malignancies. Recently, we have identified several PKK-interacting proteins, which may also play roles in the proliferation/survival of B-lymphoma cells. We are investigating (1) the function and molecular mechanism PKK in BAFF signaling (2) the function of PKK in the proliferation/survival of other B-cell malignancies in addition to DLBCL; (3) the role of PKK in B-cell malignancies in vivo and (4) function of PKK-interacting proteins in B-cell lymphomas.

Contact

Jiyong Zhao
University of Rochester
Box 633
601 Elmwood Ave.
Rochester, NY 14642
Office: MRB 2-9643
+1-585-273-1453
jiyong_zhao@urmc.rochester.edu