RUcore: Rutgers University Community Repository
Identification of phosphorylation sites of TOPORS and a role for phosphorylated residues in the regulation of ubiquitin and SUMO E3 ligase activity
Descriptive
TypeOfResource
Text
TitleInfo
(ID = T-1)
Title
Identification of phosphorylation sites of TOPORS and a role for phosphorylated residues in the regulation of ubiquitin and SUMO E3 ligase activity
SubTitle
PartName
PartNumber
NonSort
Identifier
(displayLabel = );
(invalid = )
ETD_1062
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000051763
Language
(objectPart = )
LanguageTerm
(authority = ISO639-2);
(type = code)
eng
Genre
(authority = marcgt)
theses
Subject
(ID = SBJ-1);
(authority = RUETD)
Topic
Pharmaceutical Science
Subject
(ID = SBJ-2);
(authority = ETD-LCSH)
Topic
DNA topoisomerases
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Phosphorylation
Subject
(ID = SBJ-4);
(authority = ETD-LCSH)
Topic
Ubiquitin
Subject
(ID = SBJ-5);
(authority = ETD-LCSH)
Topic
Ligases
Abstract
TOPORS is the first example of a protein that possesses both ubiquitin and SUMO E3 ligase activity. The ubiquitination activity maps to a conserved RING domain in the N-terminal region of the protein, which is not required for sumoylation activity. Similar to other E3 ligases, it is likely that the ubiquitin and sumoylation activities of TOPORS are regulated by post-translational modifications. Therefore, we employed mass spectrometry to identify post-translational modifications of TOPORS. Several putative phosphorylated regions were identified in conserved regions of the protein. We investigated the role of phosphorylation of serine 98, which is adjacent to the RING domain, in both cells and in vitro. Mutation of serine 98 to aspartic acid resulted in an increase in the ubiquitin ligase activity of TOPORS both in cells and in vitro. In addition, this mutation increased the binding of TOPORS to the E2 enzyme UbcH5a. Conversely, a phospho-deficient mutant (S98A) exhibited little change in ubiquitin ligase activity compared to wild-type TOPORS, both in cells and in vitro. Neither of the mutants affected the localization of TOPORS to punctate nuclear regions. In addition, neither mutant affected the SUMO ligase activity of TOPORS in cells or in vitro. Our findings indicate that phosphorylation of serine 98 regulates the ubiquitin but not the SUMO ligase activity of TOPORS, consistent with a potential binary switch function for TOPORS in protein ubiquitination versus sumoylation.
PhysicalDescription
Form
(authority = gmd)
electronic resource
Extent
vii, 108 p. : ill.
InternetMediaType
application/pdf
InternetMediaType
text/xml
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references (p. 99-107)
Note
(type = statement of responsibility)
by Hye-Jin Park
Name
(ID = NAME-1);
(type = personal)
NamePart
(type = family)
Park
NamePart
(type = given)
Hye-Jin
Role
RoleTerm
(authority = RULIB);
(type = )
author
DisplayForm
Hye-Jin Park
Name
(ID = NAME-2);
(type = personal)
NamePart
(type = family)
Rubin
NamePart
(type = given)
Eric
Role
RoleTerm
(authority = RULIB);
(type = )
chair
Affiliation
Advisory Committee
DisplayForm
Eric H Rubin
Name
(ID = NAME-3);
(type = personal)
NamePart
(type = family)
Suh
NamePart
(type = given)
Nanjoo
Role
RoleTerm
(authority = RULIB);
(type = )
internal member
Affiliation
Advisory Committee
DisplayForm
Nanjoo Suh
Name
(ID = NAME-4);
(type = personal)
NamePart
(type = family)
Chen
NamePart
(type = given)
Suzie
Role
RoleTerm
(authority = RULIB);
(type = )
internal member
Affiliation
Advisory Committee
DisplayForm
Suzie Chen
Name
(ID = NAME-5);
(type = personal)
NamePart
(type = family)
Kim
NamePart
(type = given)
Isaac
Role
RoleTerm
(authority = RULIB);
(type = )
outside member
Affiliation
Advisory Committee
DisplayForm
Isaac Yi Kim
Name
(ID = NAME-1);
(type = corporate)
NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB);
(type = )
degree grantor
Name
(ID = NAME-2);
(type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm
(authority = RULIB);
(type = )
school
OriginInfo
DateCreated
(point = );
(qualifier = exact)
2008
DateOther
(qualifier = exact);
(type = degree)
2008-10
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/T3HQ403V
Genre
(authority = ExL-Esploro)
ETD doctoral
Back to the top
Rights
RightsDeclaration
(AUTHORITY = GS);
(ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Notice
Note
Availability
Status
Open
Reason
Permission or license
Note
RightsHolder
(ID = PRH-1);
(type = personal)
Name
FamilyName
Park
GivenName
Hye-Jin
Role
Copyright holder
RightsEvent
(ID = RE-1);
(AUTHORITY = rulib)
Type
Permission or license
Label
Place
DateTime
Detail
AssociatedEntity
(ID = AE-1);
(AUTHORITY = rulib)
Role
Copyright holder
Name
Hye-Jin Park
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.
Back to the top
Technical
ContentModel
ETD
MimeType
(TYPE = file)
application/pdf
MimeType
(TYPE = container)
application/x-tar
FileSize
(UNIT = bytes)
1607680
Checksum
(METHOD = SHA1)
ef09e20e7d28727f6cb8f1e6875ac06460370210
Back to the top
Statistical Profile