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Characterization of Rad23, as a shuttle factor

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TitleInfo
Title
Characterization of Rad23, as a shuttle factor
Name (type = personal)
NamePart (type = family)
Okeke
NamePart (type = given)
Evelyn Ifeoma
NamePart (type = date)
1980-
DisplayForm
Evelyn Ifeoma Okeke
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RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Gartenberg
NamePart (type = given)
Marc
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Marc Gartenberg
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Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Madura
NamePart (type = given)
Kiran
DisplayForm
Kiran Madura
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Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Patel
NamePart (type = given)
Smita
DisplayForm
Smita Patel
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Haimovich
NamePart (type = given)
Beatrice
DisplayForm
Beatrice Haimovich
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
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (encoding = w3cdtf); (keyDate = yes); (qualifier = exact)
2019
DateOther (encoding = w3cdtf); (qualifier = exact); (type = degree)
2019-10
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2019
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
Abstract (type = abstract)
The ubiquitin proteasome pathway (UPP) is the primary proteolytic system for the spatial and temporal elimination of intracellular proteins, and is conserved from yeast to humans. Proteins that are targeted for degradation become covalently linked to a small protein called ubiquitin and are subsequently degraded by the 26S proteasome. Key enzymes of this pathway and their function are well characterized, but the regulation of its activities is not well understood. For instance, it is widely believed that nuclear proteins are degraded inside the nucleus despite the evidence that some nuclear proteins are degraded following their export. There were a number of discoveries regarding the site of protein turnover. First, the Madura group and others reported that the degradation of some nuclear proteins required export from the nucleus. Second, substrates were stabilized inside the nucleus when nuclear export was blocked, strongly suggesting that proteasomes do not operate inside the nucleus. Third, it was reported that catalytically active proteasomes exist predominantly in the cytosol, since purified nuclei lacked proteasome peptidase activity. Fourth, it was determined that Sts1 plays a central role in proteasome localization. Through its interaction with Srp1 (an importin-α protein), and Rpn11 (a 19S proteasome subunit), Sts1 appears to localize proteasomes to the nuclear surface. Fifth, Srp1 was shown to harbor two distinct functions; it can act as nuclear import factor, and can tether the proteasome to the nuclear surface. These findings provide a basis for a mechanism for targeting proteasomes to the nucleus. Sixth, Rad23 functions as a shuttle factor that can translocate ubiquitylated proteins to the proteasome, and is known to control the stability of the nuclear protein Rad4. The shuttle factor Rad23 is present in both the nucleus and cytosol. This suggests that Rad23 might deliver nuclear substrates to cytosolic proteasomes. Using two genetic mutants, I tested this hypothesis and found that Rad23 bound high levels of polyUb substrates when it was trapped inside the nucleus. In contrast, when it was trapped in the cytosol it interacted with low levels of polyUb substrates. Whereas previous studies examined artificial substrates, I confirmed this binding pattern using the physiological substrate Ho endonuclease, which functions in mating type switching in yeast. Therefore I propose that the function of Rad23 is to deliver nuclear substrate to proteasomes in the cytosol. The mode of nucleocytoplasmic trafficking of Rad23 remains to be discovered.
Subject (authority = RUETD)
Topic
Biochemistry
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_9425
PhysicalDescription
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application/pdf
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text/xml
Extent
1 online resource (xiii, 189 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = local)
Topic
Export
Subject (authority = local)
Topic
Rad23
Subject (authority = LCSH)
Topic
Proteins
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/t3-007a-2f74
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Okeke
GivenName
Evelyn
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-10-01 15:49:26
AssociatedEntity
Name
Evelyn Okeke
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
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.
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Type
Embargo
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-10-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2021-10-30
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 30th, 2021.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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