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Faculty Detail    
Name ANDREW JAMES PATERSON
 
Campus Address BDB 767 Zip 0012
Phone 205-975-8510
E-mail paterson@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Medicine  Med - Endocrinology, Diabetes & Metabolism Assistant Professor
Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Assistant Professor
Center  Medicine  Comprehensive Diabetes Ctr Assistant Professor
Center  Medicine  Ctr Cardiovasc Bio Assistant Professor

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 

Biographical Sketch 
Andrew James Paterson (b. 1951, Christchurch, New Zealand), citizen of the U.S.A. He received his MSc (Chemistry) from the University of Canterbury in 1975, and a PhD (Biochemistry) from the University of Otago, New Zealand in 1981. In 1981 he joined the postdoctoral fellowship program at the NIH (NCI) for 3 years and then moved to Toronto Canada as Research Associate in Dr Jeffrey Kudlow’s laboratory. In 1989 he came to UAB as Assistant Professor joining the Department of Medicine, Division of Endocrinology, with Dr. Kudlow as division director. He continued work on growth factor regulation and how O-Glycosylation regulates cellular function.

Society Memberships
Organization Name Position Held Org Link
American Physiological Society  Member   

Research/Clinical Interest
Title
Role of O-Glycosylation in Gene Regulation, Cell Growth, and Differentiation.
Description
The research in our laboratory is focused on the regulation of cell function by the O-GlcNAc post-translational modification on cellular proteins. We showed that the regulation of transforming growth factor-α gene expression by glucose was linked to the O-GlcNAc status of the ubiquitous transcription factor, Sp1. Thus, glucose-specific O-GlcNAc modification of Sp1 regulated not only TGF-α, but also a multitude of other cytoplasmic and nuclear proteins, including the proteasome, a major protein complex whose function is to get rid of unwanted cellular proteins. Our data showed that increased cellular O-GlcNAc levels reduced proteasome activity, and since some of the important cellular regulatory proteins, such as Sp1, p53, IκB, and the cyclins, are targets of the proteasome, they too can be regulated by glucose. For example, in times of low nutrition (less O-GlcNAc modification), the active proteasome degrades proteins involved in cell propagation (such as Sp1), and processes muscle proteins that are then used as an energy source. Much of our studies have involved the two principle enzymes that regulate the O-GlcNAcylation process; O-GlcNAc transferase (OGT), the enzyme that adds the O-GlcNAc moiety to proteins, and the O-GlcNAcase that removes the modification. Also, these enzymes have an additional function in that they are able to co-associate to regulate gene transcription. In particular, we showed in cell culture that nuclear hormone receptors could be suppressed or activated depending on the O-GlcNAc status of transcription factors, and that mammary tissue development was retarded in a transgenic mouse model through the suppression of estrogen receptor-dependent transcription. We have shown physiological function of modifying O-GlcNAc in other tissues, including, brain, eye and muscle, linking the phenotypes to various degenerative diseases.

Selected Publications 
Publication PUBMEDID
Xie, W., Paterson, A.J., Chin, E., Nabell, L.M., and Kudlow, J.E. Targeted expression of a dominant negative epidermal growth factor receptor in the mammary gland of transgenic mice inhibits pubertal mammary duct development. Mol Endocrinol 11, 1766-1781, 1997.  9369445 
Roos, M.D., Han, I.O., Paterson, A.J., and Kudlow, J.E. Role of glucosamine synthesis in the stimulation of TGF-alpha gene transcription by glucose and EGF. Am J Physiol 270, C803-811, 1996.  8638660 
Paterson, A.J., and Kudlow, J.E. Regulation of glutamine:fructose-6-phosphate amidotransferase gene transcription by epidermal growth factor and glucose. Endocrinology 136, 2809-2816, 1995.  7789306 
Shin, T.H., Paterson, A.J., and Kudlow, J.E. p53 stimulates transcription from the human transforming growth factor alpha promoter: a potential growth-stimulatory role for p53. Mol Cell Biol 15, 4694-4701, 1995.  7651386 
Kudlow, J.E., Leung, A.W., Kobrin, M.S., Paterson, A.J., and Asa, S.L. Transforming growth factor-alpha in the mammalian brain. Immunohistochemical detection in neurons and characterization of its mRNA. J Biol Chem 264, 3880-3883, 1989.  2645281 
  22908225 
Mueller, S.G., Paterson, A.J., and Kudlow, J.E. Transforming growth factor alpha in arterioles: cell surface processing of its precursor by elastases. Mol Cell Biol 10, 4596-4602, 1990.  2201895 
  21178104 
Ho, S.-R., Wang, K., Whisenhunt, T.R., Huang, P., Zhu, X., Kudlow, J.E., and Paterson, A.J. O-GlcNAcylation enhances FOXO4 transcriptional regulation in response to stress. FEBS Lett 584, 49-54, 2010.  19932102 
Wang, K., Ho, S.R., Mao, W., Huang, P., Zhang, F., Schwiebert, E.M., Kudlow, J.E., and Paterson, A.J. Increased O-GlcNAc causes disrupted lens fiber cell differentiation and cataracts. Biochem Biophys Res Commun 387, 70-76, 2009.  19577582 
Raja, R.H., Paterson, A.J., Shin, T.H., and Kudlow, J.E. Transcriptional regulation of the human transforming growth factor-alpha gene. Mol Endocrinol 5, 514-520, 1991.  1922084 
Zhang, F., Paterson, A.J., Huang, P., Wang, K., and Kudlow, J.E. Metabolic control of proteasome function. Physiology (Bethesda, Md) 22, 373-379, 2007.  18073410 
Zhang, F., Hu, Y., Huang, P., Toleman, C.A., Paterson, A.J., and Kudlow, J.E. Proteasome function is regulated by cyclic AMP-dependent protein kinase through phosphorylation of Rpt6. J Biol Chem 282, 22460-22471, 2007.  17565987 
Bowe, D.B., Sadlonova, A., Toleman, C.A., Novak, Z., Hu, Y., Huang, P., Mukherjee, S., Whitsett, T., Frost, A.R., Paterson, A.J., and Kudlow, J.E. O-GlcNAc Integrates the Proteasome and Transcriptome To Regulate Nuclear Hormone Receptors. Mol Cell Biol 26, 8539-8550, 2006.  16966374 
Toleman, C., Paterson, A.J., and Kudlow, J.E. Location and characterization of the O-GlcNAcase active site. Biochim Biophys Acta 1760, 829-839, 2006.  16517082 
Whisenhunt, T.R., Yang, X., Bowe, D.B., Paterson, A.J., Van Tine, B.A., and Kudlow, J.E. Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development. Glycobiology 16, 551-563, 2006.  16505006 
Toleman, C., Paterson, A.J., Whisenhunt, T.R., and Kudlow, J.E. Characterization of the histone acetyltransferase (HAT) domain of a bifunctional protein with activable O-GlcNAcase and HAT activities. J Biol Chem 279, 53665-53673, 2004.  15485860 
Liu, K., Paterson, A.J., Zhang, F., McAndrew, J., Fukuchi, K., Wyss, J.M., Peng, L., Hu, Y., and Kudlow, J.E. Accumulation of protein O-GlcNAc modification inhibits proteasomes in the brain and coincides with neuronal apoptosis in brain areas with high O-GlcNAc metabolism. J Neurochem 89, 1044-1055, 2004.  15140202 
Zhang, F., Su, K., Yang, X., Bowe, D.B., Paterson, A.J., and Kudlow, J.E. O-GlcNAc modification is an endogenous inhibitor of the proteasome. Cell 115, 715-725, 2003.  14675536 
Shin, T.H., Paterson, A.J., Grant, J.H., 3rd, Meluch, A.A., and Kudlow, J.E. 5-Azacytidine treatment of HA-A melanoma cells induces Sp1 activity and concomitant transforming growth factor alpha expression. Mol Cell Biol 12, 3998-4006, 1992.  1380648 
Liu, K., Paterson, A.J., Konrad, R.J., Parlow, A.F., Jimi, S., Roh, M., Chin, E., Jr., and Kudlow, J.E. Streptozotocin, an O-GlcNAcase inhibitor, blunts insulin and growth hormone secretion. Mol Cell Endocrinol 194, 135-146, 2002.  12242036 
Yang, X., Su, K., Roos, M.D., Chang, Q., Paterson, A.J., and Kudlow, J.E. O-linkage of N-acetylglucosamine to Sp1 activation domain inhibits its transcriptional capability. Proc Natl Acad Sci U S A 98, 6611-6616, 2001.  11371615 
Roh, M., Paterson, A.J., Asa, S.L., Chin, E., and Kudlow, J.E. Stage-sensitive blockade of pituitary somatomammotrope development by targeted expression of a dominant negative epidermal growth factor receptor in transgenic mice. Mol Endocrinol 15, 600-613, 2001.  11266511 
Liu, K., Paterson, A.J., Chin, E., and Kudlow, J.E. Glucose stimulates protein modification by O-linked GlcNAc in pancreatic beta cells: linkage of O-linked GlcNAc to beta cell death. Proc Natl Acad Sci U S A 97, 2820-2825, 2000.  10717000 
Su, K., Roos, M.D., Yang, X., Han, I., Paterson, A.J., and Kudlow, J.E. An N-terminal region of Sp1 targets its proteasome-dependent degradation in vitro. J Biol Chem 274, 15194-15202, 1999.  10329728 

Keywords
Transcription factors, gene regulation, proteasome, glycosylation, O-GlcNAc, development, transgenic mice