MARCH1: An Exploration of its Domains and Understanding its Role in the Mechanism of Antigen-Presentation and the Potential Sequela of Dysregulation

Persistent Link:
http://hdl.handle.net/10150/297769
Title:
MARCH1: An Exploration of its Domains and Understanding its Role in the Mechanism of Antigen-Presentation and the Potential Sequela of Dysregulation
Author:
Szajman, Adam Craig
Issue Date:
2013
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Current research of membrane-associated ring finger –C3HC4-1 (MARCH1) suggests that its role in mammalian immunity is more complex than was previously thought. MARCH1 is an E3 ubiquitin ligase expressed by antigen-presenting cells of the immune system, where it inhibits antigen presentation by downregulation of its substrates, MHC class II and CD86. We have studied how MARCH1 expression is regulated and determined that the protein levels are regulated, in part, through its inherent instability. We have shown that MARCH1 has distinct regions responsible for both its stability and function. The amino terminus contains a region needed for destabilization of the protein, while the amino acid residues 229-257 are missing: it appears to lead to a loss of function. Preliminary studies into dysregulation of antigen processing, inhibited by loss of MARCH1 expression in mice, have shown inclinations toward a metabolically diseased state. Knock-out (KO) MARCH1 mice have increased amounts of visceral adipose tissue relative to wild type. In addition, our preliminary results, examining transcript levels, suggest that a pro-inflammatory environment may result from the loss of MARCH1 in these fat depots, potentially resulting in metabolic disease. Our results indicate that changes in MARCH1 levels lead to a potentially dysregulated inflammatory environment.
Type:
text; Electronic Thesis
Degree Name:
B.S.
Degree Level:
bachelors
Degree Program:
Honors College; Molecular and Cellular Biology
Degree Grantor:
University of Arizona
Advisor:
Lybarger, Lonnie

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleMARCH1: An Exploration of its Domains and Understanding its Role in the Mechanism of Antigen-Presentation and the Potential Sequela of Dysregulationen_US
dc.creatorSzajman, Adam Craigen_US
dc.contributor.authorSzajman, Adam Craigen_US
dc.date.issued2013-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractCurrent research of membrane-associated ring finger –C3HC4-1 (MARCH1) suggests that its role in mammalian immunity is more complex than was previously thought. MARCH1 is an E3 ubiquitin ligase expressed by antigen-presenting cells of the immune system, where it inhibits antigen presentation by downregulation of its substrates, MHC class II and CD86. We have studied how MARCH1 expression is regulated and determined that the protein levels are regulated, in part, through its inherent instability. We have shown that MARCH1 has distinct regions responsible for both its stability and function. The amino terminus contains a region needed for destabilization of the protein, while the amino acid residues 229-257 are missing: it appears to lead to a loss of function. Preliminary studies into dysregulation of antigen processing, inhibited by loss of MARCH1 expression in mice, have shown inclinations toward a metabolically diseased state. Knock-out (KO) MARCH1 mice have increased amounts of visceral adipose tissue relative to wild type. In addition, our preliminary results, examining transcript levels, suggest that a pro-inflammatory environment may result from the loss of MARCH1 in these fat depots, potentially resulting in metabolic disease. Our results indicate that changes in MARCH1 levels lead to a potentially dysregulated inflammatory environment.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
thesis.degree.nameB.S.en_US
thesis.degree.levelbachelorsen_US
thesis.degree.disciplineHonors Collegeen_US
thesis.degree.disciplineMolecular and Cellular Biologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorLybarger, Lonnie-
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