Apolipoprotein (apoB) is secreted from liver and intestine only in association with cholesterol and triglycerides as lipoprotein particles (VLDL or chylomicrons). Since the secretion of cholesterol and apo B are coupled, an understanding of the regulation of the secretion of apo B might lead to new interventions that reduce plasma cholesterol levels. The balance between assembly and degradation accounts for the primary regulation of apo B secretion. Assembly of apo B-containing lipoprotein particles in hepatic and intestinal cells appears to occur in the endoplasmic reticulum and Golgi apparatus. Intracellular degradation of newly-synthesized apo B occurs in different locations depending on the species: in HepG2 cells, apoB at the ER is degraded, whereas in rat hepatocytes, degradation of apoB occurs after it has trafficked to the golgi. The molecular mechanisms by which apo B is sorted for assembly or degradation is not known. Translocation into the endoplasmic reticulum is one step at which regulation occurs: some molecules of apoB are bound by ubiquitin while in the Sec61 complex. The sequences in apoB and the cellular proteins that mediate this early regulatory step will be identified and characterized. Other proteins that participate in the assembly or degradation of apoB also will be sought. The overall goal of these studies is to develop a molecular view of the assembly and degradation of apo B and other secretory proteins.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL062545-04
Application #
6537583
Study Section
Metabolism Study Section (MET)
Program Officer
Applebaum-Bowden, Deborah
Project Start
1999-04-01
Project End
2004-03-31
Budget Start
2002-04-01
Budget End
2004-03-31
Support Year
4
Fiscal Year
2002
Total Cost
$374,264
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
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Hevi, Sarah; Chuck, Steven L (2003) Ferritins can regulate the secretion of apolipoprotein B. J Biol Chem 278:31924-9
Rashid, K Aftab; Hevi, Sarah; Chen, Yin et al. (2002) A proteomic approach identifies proteins in hepatocytes that bind nascent apolipoprotein B. J Biol Chem 277:22010-7