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Biochemical and physiological characterization of caspase activity in haloarchaea

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TitleInfo
Title
Biochemical and physiological characterization of caspase activity in haloarchaea
Name (type = personal)
NamePart (type = family)
Seth Pasricha
NamePart (type = given)
Mansha
NamePart (type = date)
1976-
DisplayForm
Mansha Seth Pasricha
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Bidle
NamePart (type = given)
Kay Daniel
DisplayForm
Kay Daniel Bidle
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Nanda
NamePart (type = given)
Vikas
DisplayForm
Vikas Nanda
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Kerkhof
NamePart (type = given)
Lee
DisplayForm
Lee Kerkhof
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Vetriani
NamePart (type = given)
Constantino
DisplayForm
Constantino Vetriani
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Bidle
NamePart (type = given)
Kelly Ann
DisplayForm
Kelly Ann Bidle
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (encoding = w3cdtf); (qualifier = exact)
2015
DateOther (qualifier = exact); (type = degree)
2015-01
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2015
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Caspases, cysteine aspartate-specific proteases, are key initiators and executioners of programmed cell death across a wide array of life. Archaea had been absent from the caspase inheritance discussion due to a notable lack of gene homologues with diagnostic domain signatures. Nonetheless, extremely high, basal caspase-like catalytic activity linked to the cellular stress response was recently demonstrated in the model haloarchaeon, Haloferax volcanii, and shown to be widespread among diverse phyla of archaeal extremophiles. In this dissertation, the catalytic specificity of observed caspase activity in H. volcanii was rigorously tested using hydrolytic assays with a diverse suite of canonical, fluorogenic protease substrates and inhibitors, with model serine and cysteine proteases serving as controls. It was demonstrated that H. volcanii possesses an extremely high level and highly specific caspase-like activity in exponentially growing cells that most closely resembles caspase-4. It is the dominant cellular proteolytic activity, is preferentially inhibited by a pan- caspase inhibitor, and has no cross-reactivity with other known protease families. Biochemical purification and in situ trapping with biotinylated fmk- and AOMK-based inhibitors, combined with genome-enabled proteomics and structural alignments were collectively used to identify the protein(s) that are associated with this caspase activity. These analyses identified a diverse suite of cellular proteins including thermosomes, proteasomes, a cell division protein, an ATPase (recently identified as an activator of proteasomal degradation), a putative nuclease, a putative aminopeptidase, elongation factor ╬▒EF-2, and an ornithine cyclodeaminase as key proteins associated with caspase activity. These findings biochemically connected caspase activity in H. volcanii to specific stress-related protein complexes, including those involved in the unfolded protein response (UPR). A subset of these candidate proteins were targeted for gene knockouts to empirically test their relationship to caspase activity, to assess their physiological roles, and link to UPR through incubations with canavanine. We show that loss of this activity or reduction from a critical threshold level has important consequences to organismal fitness, placing caspase activity in a novel cellular context. Given the deep archaeal roots of eukaryotes, we posit that it evolved as part of a cellular protein-quality control system, ensuring proper production, folding, and degradation.
Subject (authority = RUETD)
Topic
Microbiology and Molecular Genetics
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_6092
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xii, 138 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Catalysts
Subject (authority = ETD-LCSH)
Topic
Protease inhibitors
Note (type = statement of responsibility)
by Mansha Seth Pasricha
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/T3G162J2
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Seth Pasricha
GivenName
Mansha
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2014-12-20 16:30:12
AssociatedEntity
Name
Mansha Seth Pasricha
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
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.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2015-01-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2016-01-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after January 31st, 2016.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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