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Modulation of CD40 ligand (CD40L) expression by polypyrimidine tract-binding protein
Descriptive
TypeOfResource
Text
TitleInfo
(ID = T-1)
Title
Modulation of CD40 ligand (CD40L) expression by polypyrimidine tract-binding protein
Identifier
ETD_2584
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000053343
Language
LanguageTerm
(authority = ISO639-2);
(type = code)
eng
Genre
(authority = marcgt)
theses
Subject
(ID = SBJ-1);
(authority = RUETD)
Topic
Microbiology and Molecular Genetics
Subject
(ID = SBJ-2);
(authority = ETD-LCSH)
Topic
CD antigens
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Post-translational modification
Subject
(ID = SBJ-4);
(authority = ETD-LCSH)
Topic
T cells
Abstract
(type = abstract)
CD40 ligand (CD40L or CD154) is a protein expressed on activated CD4+ T cells, which is crucial for antibody-dependent and cell-mediated immunity. The expression of CD40L is tightly regulated at multiple levels throughout a time course of T cell activation. At the post-transcriptional level the CD40L message is rapidly degraded at early time points of activation followed by a significant increase in message stability at later times of activation (24-48 hr). Previous work from our lab revealed that a cytoplasmic polypyrimidine tract binding protein (PTB)-containing-complex binds to the CD40L 3'UTR at later times of T cell activation. To understand the direct relationship between PTB and CD40L mRNA stability and subsequently CD40L expression, we used viral RNA interference against PTB and scrambled shRNA (Control) sequence in model CD40L mRNA stability T cell line, Jurkat/D1.1. Downregulation of PTB resulted in dramatic decrease in half-life of the CD40L mRNA. The downregulation of PTB did not significantly change the percentage of CD40L+ cells, but caused an approximate 2-fold decrease in the mean fluorescence (MFI) of CD40L. Cellular fractionation of CD40L mRNA from shCTRL- and shPTB-infected cells revealed a novel role for nuclear PTB in retaining the CD40L mRNA in the nucleus. In addition, cytoplasmic PTB is important for optimal association of CD40L message with translating polysomes. Analysis of PTB cellular distribution during a time course of CD4+ T cell activation revealed cytoplasmic and nuclear localization in all resting and activated cells. However, there was an increase in cytoplasmic PTB expression at late times of activation. Binding studies revealed that CD40L mRNA is bound by nuclear PTB at all times of activation indicating that the requirements for binding of CD40L message by nuclear versus cytoplasmic PTB is highly distinct. Finally, the binding of CD40L message corresponded to a post-translational modification of cytoplasmic PTB that appears to correlate with a change in phosphorylation status of PTB. Confocal microscopy analysis of CD4+ T cells with activation-induced CD40L mRNA stability revealed co-localization of PTB and CD40L mRNA at distinct foci, suggesting a role of PTB in the localization of the stable CD40L message during T cell activation.
PhysicalDescription
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electronic resource
Extent
ix, 59 p. : ill.
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application/pdf
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text/xml
Note
(type = degree)
M.S.
Note
Includes abstract
Note
(type = bibliography)
Includes bibliographical references
Note
(type = statement of responsibility)
by Rodrigo A. Matus Nicodemos
Name
(ID = NAME-1);
(type = personal)
NamePart
(type = family)
Matus Nicodemos
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(type = given)
Rodrigo
NamePart
(type = date)
1982-
Role
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author
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Rodrigo Matus Nicodemos
Name
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NamePart
(type = family)
Covey
NamePart
(type = given)
Lori R
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chair
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Advisory Committee
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Lori R Covey
Name
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(type = personal)
NamePart
(type = family)
Kiledjian
NamePart
(type = given)
Mergerditch
Role
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(authority = RULIB)
internal member
Affiliation
Advisory Committee
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Mergerditch Kiledjian
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(type = personal)
NamePart
(type = family)
Xie
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(type = given)
Ping
Role
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(authority = RULIB)
internal member
Affiliation
Advisory Committee
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Ping Xie
Name
(ID = NAME-1);
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NamePart
Rutgers University
Role
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(authority = RULIB)
degree grantor
Name
(ID = NAME-2);
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NamePart
Graduate School - New Brunswick
Role
RoleTerm
(authority = RULIB)
school
OriginInfo
DateCreated
(qualifier = exact)
2010
DateOther
(qualifier = exact);
(type = degree)
2010
Place
PlaceTerm
(type = code)
xx
RelatedItem
(type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
(type = local)
rucore19991600001
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T3Z89CH7
Genre
(authority = ExL-Esploro)
ETD graduate
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Rights
RightsDeclaration
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(ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder
(ID = PRH-1);
(type = personal)
Name
FamilyName
Matus Nicodemos
GivenName
Rodrigo
Role
Copyright Holder
RightsEvent
(ID = RE-1);
(AUTHORITY = rulib)
Type
Permission or license
DateTime
2010-04-13 15:36:50
AssociatedEntity
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(AUTHORITY = rulib)
Role
Copyright holder
Name
Rodrigo Matus Nicodemos
Affiliation
Rutgers University. Graduate School - New Brunswick
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License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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Technical
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ETD
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application/pdf
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application/x-tar
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3870720
Checksum
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