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. (Unpublished)

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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Status:	Unpublished
Creators/Authors:	Creators Email Pitt Username ORCID Velásquez, Celestino cev10@pitt.edu CEV10 0000-0003-4049-7405
ETD Committee:	Title Member Email Address Pitt Username ORCID Committee Chair Moore, Patrick S. psm9@pitt.edu PSM9 Thesis Advisor Moore, Patrick S. psm9@pitt.edu PSM9 Committee Member Brodsky, Jeffrey L. jbrodsky@pitt.edu JBRODSKY Committee Member Thomas, Gary thomasg@pitt.edu THOMASG Committee Member Khan, Saleem A. khan@pitt.edu KHAN Committee Member Bakkenist, Christopher J. cjb38@pitt.edu CJB38
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

Available Versions of this Item

• VIRAL REGULATION OF CAP-DEPENDENT MESSENGER RNA TRANSLATION INHIBITOR 4E-BP1 DURING MITOSIS. (deposited UNSPECIFIED)
  • VIRAL REGULATION OF CAP-DEPENDENT MESSENGER RNA TRANSLATION INHIBITOR 4E-BP1 DURING MITOSIS. (deposited 12 Jul 2017 16:01) [Currently Displayed]

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