Dr. Julia Lever

Department of Biochemistry and Molecular Biology
Program in Biochemistry and Molecular Biology

University of Texas-Houston Medical School
P.O. Box 20708 - Houston, Texas 77225
(713) 500-6055 - Fax (713)-500-0652
email: Julia.E.Lever@uth.tmc.edu

Ph.D., Univeristy of California, Berkeley
Postdoctoral Fellowship, University of California
San Diego
Merit Award, National Institutes of Health

Regulation of Differentiated Gene Expression

The development and maintenance of a differentiated epithelial cell phenotype requires a complex series of interactions between the genome and the cellular environment. Steady state levels of a messenger RNA, and thus its protein product, are regulated by a balance between its rate of synthesis after transcriptional activation of the gene promoter and its rate of post-transcriptional degradation by cellular nucleases. It is now apparent that both processes are tightly regulated in response to hormonal signaling cascades by a protein phosphoryla-tion- dependent process that involves specific recognition of cis-acting nucleotide sequences by cellular proteins.

My laboratory's longstanding interest in structure, function and gene regulation of epithelial cell glucose transporters is now focused on the mechanism of transporter message stabilization after cyclic AMP elevation or differentiation inducer treatment. The scheme below describes our current hypothesis: binding of a phosphoprotein to a specific sequence in the 3' untranslated region of the transporter mRNA leads to message stabilization and transporter up-regulation.

Selected References

Loflin, P. and Lever, J.E. Cyclic nucleotide-dependent screening of a lambda expression library for nucleic acid binding activities. BioTechniques 32: 1020-1028 (2002).

Loflin, P. and Lever, J. E. HuR Binds a Cyclic Nucleotide-Dependent, Stabilizing Domain in the 3' Untranslated Region of Na+/Glucose
Cotransporter (SGLT1) mRNA, FEBS Lett. 509, 267-271 (2001).

Loflin, P., and Lever, J.E. A Cis-dominant cyclic nucleotide-dependent regulatory Domain in the 3' untranslated region of Na+/glucose cotransporter (SGLT1) mRNA, FEBS Lett. 492, 233-237, (2001).

S Clancey CJ and Lever JE: Differential regulation of three glucose transporter genes in a renal epithelial cell line. J. Cell. Physiol. 185:244-252, 2000.

Lee W-Y, Loflin P, Clancey CJ, Peng H and Lever JE: Cyclic nucleotide regulation of Na+/glucose cotransporter (SGLT1) mRNA stability: Interaction of a nucleocytoplasmic protein with a regulatory domain in the 3' untranslated region critical for stabilization, J. Biol. Chem. 275: 33998-34008, 2000.

Lever JE, Lee WY, Clancey CJ and Loflin P: Post-transcriptional regulation of Na/glucose cotransporter expression. in Control and Diseases of Sodium Dependent Transport Proteins and Ion Channels, Y. Suketa, E. Carafoli, M. Lazdunski, K. Mikoshiba, Y. Okada and E. M. Wright, eds. Elsevier: pp. 347-354, 2000.