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Ricin-A-chain (RTA) inhibits the unfolded protein response (UPR) in mammalian cells

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TypeOfResource
Text
TitleInfo (ID = T-1)
Title
Ricin-A-chain (RTA) inhibits the unfolded protein response (UPR) in mammalian cells
Identifier
ETD_2861
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000056855
Language
LanguageTerm (authority = ISO639-2); (type = code)
eng
Genre (authority = marcgt)
theses
Subject (ID = SBJ-1); (authority = RUETD)
Topic
Nutritional Sciences
Subject (ID = SBJ-2); (authority = ETD-LCSH)
Topic
Ricin--Analysis
Subject (ID = SBJ-3); (authority = ETD-LCSH)
Topic
Ricin--Denaturation
Subject (ID = SBJ-4); (authority = ETD-LCSH)
Topic
Cell-mediated cytotoxicity
Abstract (type = abstract)
Ricin, a type II ribosome-inactivating protein, has been used as a biochemical weapon due to its ability to inhibit protein synthesis and induce cytotoxicity. The unfolded protein response (UPR) is a survival response that helps cells to recover from stress that occurs following the accumulation of misfolded proteins in the ER. Failure to recover from ER stress can lead to apoptosis. In yeast, ricin-A-chain (RTA), the enzymatic component of ricin, inhibits the unfolded protein response (UPR). However, the ability of RTA to affect UPR has not been investigated in mammalian cells. The goals of this project were to determine if RTA could inhibit the UPR in mammalian cells and if altering the UPR affected RTA cytotoxicity. The UPR consists of three signaling cascades, IRE1, PERK, and ATF6. In HeLa cells, a human cervical carcinoma cell line, we found that RTA could inhibit tunicamycin (Tm)-induced IRE1 phosphoryation and XBP-1 mRNA splicing at 4 h. A similar effect was observed in the non-transformed mammary epithelial cell line MAC-T. RTA also inhibited the ability of dithiothreitol (DTT) to activate the PERK pathway in HeLa cells, as shown by inhibition of DTT-induced eIF2α phosphorylation at 4 h. In both cell types, RTA decreased expression of the downstream chaperone BiP in response to Tm. To determine if inhibition of the IRE1 and PERK pathways by RTA affected its cytotoxicity, cells were treated with RTA in combination with DTT or Tm. Cleavage of both caspase-3 and -7 was greater in both HeLa and MAC-T cells when they were treated with RTA and DTT or RTA and Tm compared to cells treated with RTA, DTT, or Tm alone. These results indicate that RTA is more cytotoxic when UPR is inhibited.
PhysicalDescription
Form (authority = gmd)
electronic resource
Extent
vii, 64 p. : ill.
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application/pdf
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text/xml
Note (type = degree)
M.S.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Chao-Ting Wang
Name (ID = NAME-1); (type = personal)
NamePart (type = family)
Wang
NamePart (type = given)
Chao-ting
NamePart (type = date)
1982-
Role
RoleTerm (authority = RULIB)
author
DisplayForm
Chao-ting Wang
Name (ID = NAME-2); (type = personal)
NamePart (type = family)
Cohick
NamePart (type = given)
Wendie S.
Role
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chair
Affiliation
Advisory Committee
DisplayForm
Wendie S. Cohick
Name (ID = NAME-3); (type = personal)
NamePart (type = family)
Storch
NamePart (type = given)
Judith
Role
RoleTerm (authority = RULIB)
internal member
Affiliation
Advisory Committee
DisplayForm
Judith Storch
Name (ID = NAME-4); (type = personal)
NamePart (type = family)
Igal
NamePart (type = given)
Ariel
Role
RoleTerm (authority = RULIB)
internal member
Affiliation
Advisory Committee
DisplayForm
Ariel Igal
Name (ID = NAME-1); (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (ID = NAME-2); (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
OriginInfo
DateCreated (qualifier = exact)
2010
DateOther (qualifier = exact); (type = degree)
2010-10
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
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3VQ32DF
Genre (authority = ExL-Esploro)
ETD graduate
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RightsDeclaration (AUTHORITY = GS); (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
Wang
GivenName
Chao-ting
Role
Copyright Holder
RightsEvent (ID = RE-1); (AUTHORITY = rulib)
Type
Permission or license
DateTime
2010-09-15 09:28:59
AssociatedEntity (ID = AE-1); (AUTHORITY = rulib)
Role
Copyright holder
Name
Chao-ting Wang
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject (ID = AO-1); (AUTHORITY = rulib)
Type
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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ETD
MimeType (TYPE = file)
application/pdf
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application/x-tar
FileSize (UNIT = bytes)
3737600
Checksum (METHOD = SHA1)
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