Participating Faculty
Nancy Magnuson

Professor
School of Molecular Biosciences
Washington State University
Pullman, WA 99164-4234

Ph.D., 1978
Washington State University

Phone: 509-335-0966
Email: magnuson@mail.wsu.edu

 

Research Interests:
Cancer Research

Research Summary:

We are interested how the proto-oncogene called pim-1, which codes for a serine/threonine kinase, is involved in the molecular mechanisms of proliferation and differentiation of lymphoid, myeloid and epithelial cells. In the adult, Pim-1 expression is limited to these cell types and to germ cells. Our laboratory has identified three targets of Pim-1: a tyrosine phosphatase (PTP-U2S) important in differentiation, nuclear mitotic apparatus (NuMA) protein important in cell division and a CDC kinase inhibitor (p21Cip1/WAF1) important in halting DNA replication to allow DNA repair. Because Pim-1 is oncogenic when over expressed, we are also interested in understanding how Pim-1 contributes cancer production. During the course of our studies, we have discovered that Pim-1 expression is highly regulated at multiple levels: transcriptional, post-transcriptional, translational and post-translational. This high degree of regulation suggests that Pim-1 kinase levels need to be precisely controlled for normal cellular activity because over expression can lead to cancer. Interestingly, Pim-1 is best described as a weak oncogene. By itself, it does not induce cancer very efficiently, but when it is continuously over expressed with a second oncogene such as c-myc, the two genes synergize and become extremely oncogenic. Therefore, besides determining the normal function of Pim-1, we are also interested in determining mechanistically how Pim-1 and other oncoproteins such as c-Myc synergize to cause cancer.
 
Representative Publications:

Watts, R. J., D. Washington, J. Howsawkeng, F. J. Loge, and A. Borg, K.E., M. Zhang, D. Hegge, R.L. Stephen, D.J. Buckley, N.S. Magnuson, and A.R. Buckley. 1999. Prolactin regulation of pim-1 expression: positive and negative promoter elements. Endocrinol. 140: 5659-5668.

Wang, Z, K. Petersen, M.S. Weaver and N.S. Magnuson. 2001. cDNA cloning, sequencing and characterization of bovine pim-1. Vet. Immunol. Immunopath. 78:179-197.

Wang, Z., N. Bhattacharya, M. Meyers, H. Seimiya, T. Tsuruo, J.A. Tonani and N.S. Magnuson. 2001. Pim-1 kinase negatively reglates the activity of PTP-U2S phosphatase and influences terminal differentiation and apoptosis of monoblastoid leukemia cells. Arch. Biochem. Biophys. 390:9-18.

Zhu, N., L.M. Ramirez, R.L. Lee, N.S. Magnuson, G.A. Bishop, and M.R. Gold. 2002. CD40 signaling in B cells regulates the expression of the Pim-1 kinase via the NF-kB pathway.
J Immunol. 168:744-754.

Bhattacharya, N., Z. Wang, C. Davitt, I.F.C. McKenzie, P. Xing and N.S. Magnuson. 2002. Pim-1 associates with protein complexes necessary for mitosis. Chromasoma 111:80-95.

Wang, Z., N. Bhattacharya, P.F. Mixter, W. Wei, J. Sedivy and N.S. Magnuson. 2002. Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1 kinase. Biochem. Biophys. Acta 217:45-55.

Weaver, M., K. Petersen, and N.S. Magnuson. 2002. The internal ribosome entry site of the pim-1 proto-oncogene provides a translational advantage under the pro-apoptotic and stress conditions. J. Biol. Chem. (In press)

Bankhead, A., N.S. Magnuson and R.B. Heckendorn. 2004. Modeling multicellular and tumorous existence with genetic cellular automata. Simulation and Synthesis of Living Systems (ALIFE9).

Shay, K.P., Z. Wang, P.-X. Xing, I.F.C. McKenzie and N.S. Magnuson. 2005. Pim-1 kinase stability and activity is regulated by heat shock proteins. Mol. Cancer Res. 3:170-181.

Wang, Z., M. Weaver, M. and N.S. Magnuson. 2005. The 5’-UTR of Pim-1 kinase contains cryptic promoter activity but not IRES activity. Nucleic Acids Research 33:2248-2258.

Dement, G.A., N.R. Treff, N.S. Magnuson, V. Franceschi, and R. Reeves. 2005. Nuclear transcription factor HMGA1 enters mitochondria and binds to mitochondrial DNA in vivo. Exp Cell Res. 307:388-401.