Request for Funding

Medical Student Research Fellowship for Summer 2001

Mentor: Sandy Hofmann
Department: Internal Medicine/Hamon Center for Therapeutic Oncology Research
Room number: NB8.104A
Mail Code: 8593
Phone number: 214-648-4911
E-mail: Sandra.Hofmann@UTSouthwestern.edu
Project title: Regulation of PPT1 by SREBPs

Human subjects IRB approved project number (where applicable): na

Animal subjects IRB approved project number (where applicable): (don't you mean IACRAC?) 0433-00-08-1

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) Basic (some handling of animal tissues may be involved))

Brief Description of Project:

Palmitoyl-protein thioesterase-1 (PPT1) is an enzyme that removes the fatty acid palmitate from fatty acylated proteins. In a recent screen of mRNA transcripts from the livers of mice overexpressing SREBP-1, a "master" regulator of cholesterol and fatty acid metabolism, it was noted that PPT1 was one of the most highly up-regulated genes in this tissue. This was unexpected because PPT1 is a lysosomal enzyme with normally low expression in the liver. Lysosomal enzymes are considered to be "housekeeping" enzymes and are generally unregulated by physiological stimuli.

The first goal of this project will be to confirm the upregulation of PPT1 in transgenic SREBP1 livers. Other available tissues will also be examined. If the upregulation is confirmed, promotor elements upstream of the PPT1 gene will be systematically examined experimentally for regulatory elements that respond to SREBP. Identification of such an element would provide direct evidence that PPT1 is regulated by SREBP1, and would suggest an unexpected role for PPT1 in lipid metabolism.

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