The Regulation and Function of Cyclin Dependent Kinase 11 (CDK11): Analysis of the Cdc2L1 PPromoter and Elucidation of CDK11p58 Function During Mitosis

Persistent Link:
http://hdl.handle.net/10150/193606
Title:
The Regulation and Function of Cyclin Dependent Kinase 11 (CDK11): Analysis of the Cdc2L1 PPromoter and Elucidation of CDK11p58 Function During Mitosis
Author:
Kahle, Amber C
Issue Date:
2006
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Cancer is a disease that is characterized by genetic mutations that occur leading to an increased propensity for abnormal cellular growth. Chromosome 1p36.3 is lost or aberrant in several tumor types, including neuroblastoma and melanoma. In order to understand the functional significance of chromosome 1p36.3 loss in tumors, our research has been focused on elucidating the function of cyclin dependent kinase 11 (CDK11), a gene that is located within this chromosomal region. CDK11 is a serine/threonine kinase and is a member of the p34cdc2-related family of kinases. CDK11 has multiple isoforms that are involved RNA processing, apoptosis and the cell cycle.CDK11 proteins are encoded by two different genes (Cdc2L1 and Cdc2L2), which are highly homologous to each other and are evolutionarily conserved. Our studies originated from investigating the regulation of the expression of CDK11 genes by isolating and characterizing the Cdc2L1 promoter region. We identified the basal promoter region and found that Cdc2L1 is regulated by transcription factors Ets-1, Skn-1 and E2F-1. Conversely, Cdc2L2 was shown to be regulated by TCF11/Nrf2, Ets-1 and CREB, displaying differential regulation of the two different CDK11 genes.CDK11p58 is generated during the G2/M phase of the cell cycle because of an internal ribosome entry site found within the full-length CDK11 transcript. The generation of CDK11p58 during the cell cycle had previously been shown to be a regulatory event; however the actual function of CDK11p58 remained unknown. Our research focused on determining potential interaction partners of CDK11p58 and elucidating the role of these interactions in the regulation of the cell cycle. Utilizing proteomic technology, we were able to find multiple potential interacting proteins with CDK11p58, including a RNA-dependent RNA helicase protein, DDX15. DDX15 is phosphorylated by CDK11p58 and both proteins are directly involved in cell cycle regulation. Additionally, CDK11p58 was found to associate with several cytoskeletal proteins, alpha- and beta-tubulin, lamin A, and vimentin, and heat shock proteins, Hsp70 and Hsp90. These investigations are only preliminary but provide a novel insight into the possible function of CDK11p58 during mitosis.
Type:
text; Electronic Dissertation
Keywords:
Cancer biology
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Cancer Biology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Nelson, Mark A.
Committee Chair:
Nelson, Mark A.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleThe Regulation and Function of Cyclin Dependent Kinase 11 (CDK11): Analysis of the Cdc2L1 PPromoter and Elucidation of CDK11p58 Function During Mitosisen_US
dc.creatorKahle, Amber C.en_US
dc.contributor.authorKahle, Amber Cen_US
dc.date.issued2006en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractCancer is a disease that is characterized by genetic mutations that occur leading to an increased propensity for abnormal cellular growth. Chromosome 1p36.3 is lost or aberrant in several tumor types, including neuroblastoma and melanoma. In order to understand the functional significance of chromosome 1p36.3 loss in tumors, our research has been focused on elucidating the function of cyclin dependent kinase 11 (CDK11), a gene that is located within this chromosomal region. CDK11 is a serine/threonine kinase and is a member of the p34cdc2-related family of kinases. CDK11 has multiple isoforms that are involved RNA processing, apoptosis and the cell cycle.CDK11 proteins are encoded by two different genes (Cdc2L1 and Cdc2L2), which are highly homologous to each other and are evolutionarily conserved. Our studies originated from investigating the regulation of the expression of CDK11 genes by isolating and characterizing the Cdc2L1 promoter region. We identified the basal promoter region and found that Cdc2L1 is regulated by transcription factors Ets-1, Skn-1 and E2F-1. Conversely, Cdc2L2 was shown to be regulated by TCF11/Nrf2, Ets-1 and CREB, displaying differential regulation of the two different CDK11 genes.CDK11p58 is generated during the G2/M phase of the cell cycle because of an internal ribosome entry site found within the full-length CDK11 transcript. The generation of CDK11p58 during the cell cycle had previously been shown to be a regulatory event; however the actual function of CDK11p58 remained unknown. Our research focused on determining potential interaction partners of CDK11p58 and elucidating the role of these interactions in the regulation of the cell cycle. Utilizing proteomic technology, we were able to find multiple potential interacting proteins with CDK11p58, including a RNA-dependent RNA helicase protein, DDX15. DDX15 is phosphorylated by CDK11p58 and both proteins are directly involved in cell cycle regulation. Additionally, CDK11p58 was found to associate with several cytoskeletal proteins, alpha- and beta-tubulin, lamin A, and vimentin, and heat shock proteins, Hsp70 and Hsp90. These investigations are only preliminary but provide a novel insight into the possible function of CDK11p58 during mitosis.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectCancer biologyen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineCancer Biologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorNelson, Mark A.en_US
dc.contributor.chairNelson, Mark A.en_US
dc.contributor.committeememberBosco, Giovannien_US
dc.contributor.committeememberMartinez, Jesseen_US
dc.contributor.committeememberSchroeder, Joyceen_US
dc.contributor.committeememberParker, Royen_US
dc.identifier.proquest1863en_US
dc.identifier.oclc659746414en_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.