JOHN L. CLEVELAND
ASSISTANT PROFESSOR

EDUCATION:
B.S. 1979, University of Maine, Orono (Biology)
Ph.D. 1985, Wayne State University School of Medicine, Detroit (Immunology & Microbiology)

RESEARCH INTERESTS: Our laboratory has focused on the regulation and function of the c-myc proto-oncogene, a nuclear phosphoprotein which is a common target for activation in human neoplasia. Deregulated c-myc expression suppresses cell cycle arrest and promotes G1 progression into S phase in the absence of signals normally required for proliferation. The ability of c-myc to promote deregulated cell growth has been proposed to be due to its ability to function as a transcription factor. Our laboratory has identified a gene target for c-myc which is itself required for G1 progression and have shown that myc is a potent trans-activator of the promoter of this gene. Current research is focusing on the mechanism by which c-myc regulates this target and to identify myc-specific interactive proteins which augment or repress this activity.

CURRENT RESEARCH SUPPORT:
RO1 DK-44158 "c-myc Function in Myeloid Cell Growth and Differentiation" September 1, 1991 - August 31, 1996; $482,936 TDC

PUBLICATIONS:
Dean, M., Cleveland, J.L., Rapp, U.R and Ihle, J.N. (1987) Role of myc in the abrogation of IL-3 dependence of myeloid FDC-P1 cells. Oncogene Res., 1, 279-296.
Farrar, W.L., Evans, S., Rapp, U.R., and Cleveland, J.L. (1987) Effects of anti-proliferative cAMP on interleukin-2 stimulated gene expression. J. Immunol., 139, 2075-2080.
Farrar, W.L., Harel-Bellan, A., Cleveland, J.L., and Vinocour, M. (1988) Regulation of ornithine decarboxylose activity by interleukin 2 and cyclic AMP. J. Immunol., 141, 967-971.
Cleveland, J.L., Huleihel, M., Bressler, P., Siebenlist, U., Akiyama, W., Eisenman, R., and Rapp, U.R. (1988) Negative regulation of c-myc transcription involves myc family proteins. Oncogene Res., 3, 357-375.
Weinstein, Y., Morishita, K., Cleveland, J.L., and Ihle, J.N. (1989) Interleukin-3 (IL-3) induces transcription from nonrearranged gamma T-cell receptor loci in IL-3 dependent cell lines. J. Exp. Med., 169, 2059-2071.
Cleveland, J.L., Dean, M., Rosenberg, N., Wang, J.Y.J., and Rapp, U.R. (1989) Tyrosine kinase oncogenes abrogate interleukin-3 dependence of murine myeloid cells through signalling pathways involving c-myc:: conditional regulation of c-myc transcription by temperature-sensitive v-abl. Mol. Cell. Biol., 9, 5685-5695.
Storm, S.M., Cleveland, J.L., and Rapp, U.R. (1989) Expression of raf family proto-oncogenes in normal mouse tissues. Oncogene, 5, 345-351.
Heidecker, G., Huleihel, M., Cleveland, J.L., Kolch, W., Beck, T.W., Lloyd, P., Pawson, T., and Rapp, U.R. (1990) Mutational activation of c-raf-1 and definition of the minimal trans-forming sequence. Mol. Cell Biol., 10, 2503-2512.
Beck, T.W., Brennscheidt, U., Sithanandam, G., Cleveland, J., and Rapp, U.R. (1990) Molecular organization of the human raf-1 promoter region. Mol. Cell Biol., 10, 3325-3333.
Principato, M.A., Cleveland, J.L., Rapp, U.R., Holmes, K.L., Pierce, J.H., Morse, H.C. III, and Klinken, S.P. (1990) Transformation of murine bone marrow cells with combined v-raf/v-myc oncogenes yields clonally related mature B cells and macrophages. Mol. Cell Biol., 10, 3562-3568.
Kolch, W., Cleveland, J.L., and Rapp, U.R. (1991) Role of oncogenes in the abrogation of growth factor requirements of hemopoietic cells. In W.R. Paukovits (Ed.) Crit. Rev. Cancer. CRC Press, 279-304.
Katzav, S., Cleveland, J.L., Heslop, H.E., and Pulido, D. (1991) Loss of the aminoterminal helix-loop-helix domain of the vav proto-oncogene activates its transforming potential. Mol.Cell Biol., 11, 1912-1920.
Askew, D.S., Ashman, R.A., Simmons, B.C., and Cleveland, J.L. (1991) Constitutive c-myc expression in an IL-3 dependent myeloid cell line suppress cell cycle arrest and accelerates apoptosis. Oncogene, 6, 1915-1922.
Roussel, M.F., Cleveland, J.L., Shurtleff, S.A., and Sherr, C.J. (1991) Myc rescue of a mutant CSF-1 receptor impaired in mitogenic signaling. Nature, 353, 361-363.
Yi, T., Cleveland, J.L., and Ihle, J.N. (1992) A protein tyrosine phosphatase containing SH2 domains: Characterization, preferential expression in hematopoietic cells and localization to human chromosome 12p12-13. Mol. Cell Biol., 12, 836-846.
Rock, C.O., Cleveland, J.L., and Jackowski, S. (1992) Macrophage growth arrest by cyclic AMP defines a distinct checkpoint in the Mid-G7 stage of the cell cycle and overrides constitutive c-myc expression. Mol. Cell Biol.,12, 2351-2358.
Duyao, M.P., Kessler, D.J., Spicer, D.B., Bartholomew, C., Cleveland, J.L., and Sonnenshein, G.E. (1992) Transactivation of the c-myc promoter by the HTLV-1 tax gene. J. Biol. Chem., 267, 16288-16291.
Okuda, T., Cleveland, J.L. and Downing, J.R. (1992) PICTAIRE-1 and PICTAIRE-3, two members of a novel ded2/CDC 28-related protein kinase gene family. Oncogene, 7, 2249-2258.
Miura, O., Cleveland, J.L., and Ihle, J.N. (1993) Inactivation of the erythopoietin receptor by point mutations in a region showing homology with other cytokine receptors. Mol. Cell Biol. ,13, 1788-1795.
Bello-Fernandez, C., Packham, G., and Cleveland, J.L. (1993) Ornithine decarboxylase is a transcriptional target of c-myc. Proc. Natl, Acad. Sci., 90, 7804-7808.
Askew, D.S., Ihle, J.N., and Cleveland, J.L. (1993) Activation of apoptosis associated with enforced myc expression in myeloid progenitor cells is dominant to the suppression of apoptosis by Interleukin-3 or erythopoietin. Blood, 82, 2079-2987.
Silvennoinen, O., Witthuhn, B.A., Quelle, F.W., Cleveland, J.L., Yi, T., and Ihle, J.N. (1993) Structure of the murine JAK2 protein tyrosine kinase and its role in IL-3 signal transduction. Proc. Natl. Acad. Sci., 90, 8429-8433.
Cleveland, J.L., Troppmair, J., Packham, G., Askew, D.S., Lloyd, P., Ihle J.N., and Rapp, U.R. (1994) v-raf suppresses apoptosis and promotes growth of Interleukin-3-dependent myeloid cells. Oncogene, 9, 2217-2226.
Packham, G. and Cleveland, J.L. (1994) Ornithine decarboxylase is a mediator of c-Myc-induced apoptosis.
Mol. Cell. Biol., 9, 5741-5747.
Packham G., Bello Fernandez, C., and Cleveland J.L. (1994) Position and orientation independent transactivation by c-Myc. Cell. Mol. Biol. Res., 40, 699-706.
Packham, G. and Cleveland, J.L. (1995) c-Myc and apoptosis. BBA Reviews on Cancer, 1242 (1), 11-29.
Cleveland, J.L. and Ihle, J.N. (1995) Contenders in Fas/TNF Death Signalling. Cell., 81, 479-482.
Katzav, S. Packham, G., Sutherland, M., Aroca, P., Santos, E., and Cleveland, J.L. (1995) Vav and ras induce fibroblast transformation by overlapping signaling pathways which require c-myc function. Oncogene, 11, 1079-1088.
Hiebert, S.H., Packham, G., Strom, D., Haffner, R., Oren, M., Zambetti, G., and Cleveland, J.L. (1995) E2F-1:DP-1 induces p53 and overrides survival factors to trigger apoptosis. Mol. Cell. Biol., submitted.