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Exploring the Stability and Degradation of the Lipin 1 Protein

Presenters Name: 
Faye Giebink
Co Presenters Name: 
Primary Research Mentor: 
Thurl Harris
Secondary Research Mentor: 
Time: 
11:00 - 12:15
Time of Presentation: 
2019 - 11:00am to 12:15pm
Session: 
2
Location: 
Newcomb Hall Ballroom
Presentation Type: 
Poster
Presentations Academic Category: 
Science
Grant Program Recipient: 
Harrison Undergraduate Research Grant
Abstract: 

Lipin-1 plays a central role in the regulation of lipid metabolism, which is crucial to maintaining systemic energy homeostasis in the body. Lipin-1 functions as a phosphatidic acid phosphatase to convert phosphatidic acid (PA) to diacylglycerol (DAG) as part of the Kennedy pathway. The polybasic domain (PBD) of lipin-1 is a stretch of nine contiguous Arg and Lys residues within the central domain that are essential for interaction with PA. Mutation of these residues to Ala greatly increases protein expression of lipin-1. We show that this increase in expression is due to an increase in protein half-life and we suggest this is due to alterations in lipin-1 ubiquitination and proteasomal degradation. During proteomic analysis of lipin-1 we identified at least one Lys within the PBD as acetylated. Acetylated Lys cannot be ubiquitinated. We have previously demonstrated an interaction between lipin-1 and HDAC1 and 3 and lipin-1, and so we treated cells with Trichostatin A (TSA) to prevent the removal of acetyl groups and cause the accumulation of hyperacetylated lipin-1. We find that pre-treatment of cells with TSA increases lipin-1 protein half-life. We hypothesize that the accumulation of acetylated Lys within the PBD may prevent lipin-1 ubiquitination and degradation. Alternatively, lipin-1 acetylation may affect stability through Lys residues outside of the PBD or through other mechanisms, such as altering phosphorylation. Understanding what regulates lipin-1 stability and its role as a magnesium-dependent phosphatide phosphatase (PAP) enzyme in triacylglycerol synthesis is important to comprehend mechanisms involved in metabolic disorders that lead to obesity.