Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/79687
Title: THE INTERPLAY BETWEEN ARF AND TRIM28 IN TUMOR SUPPRESSION
Authors: NEO SHU HUI
Keywords: ARF, TRIM28, centrosome, cancer, sumoylation, NPM1
Issue Date: 25-Aug-2014
Source: NEO SHU HUI (2014-08-25). THE INTERPLAY BETWEEN ARF AND TRIM28 IN TUMOR SUPPRESSION. ScholarBank@NUS Repository.
Abstract: THE TUMOR SUPPRESSOR ARF IS KNOWN TO ENHANCE SUMOYLATION, HOWEVER, THE PHYSIOLOGICAL FUNCTION OF ARF-MEDIATED SUMOYLATION IS STILL UNCLEAR DUE TO THE LACK OF IDENTIFICATION OF THE ASSOCIATED E3 SUMO LIGASE. HERE WE IDENTIFIED TRIM28/KAP1 AS A NOVEL ARF-BINDING PROTEIN AND SUMO E3 LIGASE FOR SUMOYLATION OF NPM1/B23. NPM1 SUMOYLATION WAS ATTENUATED BY TRIM28 DEPLETION AND ENHANCED BY TRIM28 OVEREXPRESSION. INTERESTINGLY, OVEREXPRESSION OF ARF AND TRIM28 PROMOTED CENTROSOMAL LOCALIZATION OF NPM1 BY ENHANCING SUMOYLATION AND REDUCED CENTROSOME AMPLIFICATION DEPENDENT ON THE E3 LIGASE ACTIVITY OF TRIM28. CONVERSELY, DEPLETION OF ARF OR TRIM28 INCREASED CENTROSOME AMPLIFICATION. IMPORTANTLY, ARF COUNTERACTED ONCOGENIC RAS-INDUCED CENTROSOME AMPLIFICATION. CENTROSOME AMPLIFICATION IS OFTEN INDUCED BY ONCOGENIC INSULTS, LEADING TO GENOMIC INSTABILITY. HOWEVER, THE PROTECTIVE MECHANISMS BY TUMOR SUPPRESSORS TO PREVENT THIS ARE POORLY UNDERSTOOD. OUR FINDINGS SUGGEST A NOVEL ROLE OF ARF-INDUCED
URI: http://scholarbank.nus.edu.sg/handle/10635/79687
Appears in Collections:Ph.D Theses (Open)

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