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VIRAL REGULATION OF CAP-DEPENDENT MESSENGER RNA TRANSLATION INHIBITOR 4E-BP1 DURING MITOSIS

Velásquez, Celestino (2017) VIRAL REGULATION OF CAP-DEPENDENT MESSENGER RNA TRANSLATION INHIBITOR 4E-BP1 DURING MITOSIS. Doctoral Dissertation, University of Pittsburgh.

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Abstract

The work described in this dissertation started in 2013 and focuses on the activation of cap-dependent mRNA translation and regulation of the translation inhibitor protein 4E-BP1 during mitosis. By investigating the viral oncoprotein Merkel cell polyomavirus small T antigen (MCV sT), an alternative pathway for cap-dependent mRNA translation regulation through the CDK1 kinase was discovered. In addition, a novel phosphorylation site of 4E-BP1—Ser83—was identified in mitotic cells, and a polyclonal antibody against this phosphorylation site was generated. The phospho-Ser83 4E-BP1 antibody is a useful tool that can be used as a bona fide mitotic marker by various assays: immunoblotting, immunofluorescence, and flow cytometry. Overall, this work provokes a reassessment of protein synthesis regulation during cell division, hints at additional undescribed functions for 4E-BP1, and suggests that certain mRNAs translated in this phase of the cell cycle may contribute to cell proliferation and tumorigenesis.


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Details

Item Type: University of Pittsburgh ETD
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Velásquez, Celestinocev10@pitt.eduCEV100000-0003-4049-7405
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMoore, Patrick S.psm9@pitt.eduPSM9
Thesis AdvisorMoore, Patrick S.psm9@pitt.eduPSM9
Committee MemberBrodsky, Jeffrey L.jbrodsky@pitt.eduJBRODSKY
Committee MemberThomas, Garythomasg@pitt.eduTHOMASG
Committee MemberKhan, Saleem A.khan@pitt.eduKHAN
Committee MemberBakkenist, Christopher J.cjb38@pitt.eduCJB38
Date: 12 July 2017
Date Type: Publication
Defense Date: 12 June 2017
Approval Date: 12 July 2017
Submission Date: 14 June 2017
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 177
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Integrative Molecular Biology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Merkel cell, Merkel cell polyomavirus, small T antigen, tumor viruses, cancer, 4E-BP1, cyclin-dependent kinase 1, mammalian target of rapamycin, mitosis, cap-dependent mRNA translation
Date Deposited: 12 Jul 2017 16:01
Last Modified: 12 Jul 2017 16:01
URI: http://d-scholarship.pitt.edu/id/eprint/32714

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