{"id":{"repo_id":"vcu","oai_identifier":"oai:scholarscompass.vcu.edu:etd-1480"},"canonical_url":"https://search.dev.ndltd.org/etd/vcu/oai:scholarscompass.vcu.edu:etd-1480","repository":{"repo_id":"vcu","name":"Virginia Commonwealth University","base_url":"https://scholarscompass.vcu.edu/do/oai/"},"display":{"title":"Defining the functions of a conserved hydrophobic domain in the ARF tumor suppressor","abstract":"The INK4A-ARF locus encodes two tumor suppressors; p16 and p19Arf, both of which restrain cell growth by regulating the functions of Retinoblastoma (Rb) and p53 respectively. Throughout development, p19Arf is kept at minimal levels, but under conditions of oncogenic stress, p19Arf expression is induced and its tumor suppressive activities are mediated through the stabilization of p53 or in a p53-independent manner. Introducing a point mutation (L46D) into the conserved hydrophobic domain (37-51) in p19Arf annulled ARF/CtBP2 interaction and mediated cell survival by rendering cells irresponsive to apoptosis. In vivo analysis on the percentage of lymphoma free survivals in ARFL46D/L46D mice indicated that disrupting ARF/CtBP2 binding resulted in a tumor spectrum similar to that in ARF-null mice. In this study, we characterized the functions of the hydrophobic domain of ARF in MEF cells under genotoxic stress, ultra-violet irradiation and oncogene activation. We demonstrated that cells bearing the mutation showed decreased responsiveness to H-RasV12 induced senescence consistent with p21 deficiency. We speculate that the deficit in p21 expression is possibly caused by CtBP2 repressive and oncogene -like properties.","abstract_html":"The INK4A-ARF locus encodes two tumor suppressors; p16 and p19Arf, both of which restrain cell growth by regulating the functions of Retinoblastoma (Rb) and p53 respectively. Throughout development, p19Arf is kept at minimal levels, but under conditions of oncogenic stress, p19Arf expression is induced and its tumor suppressive activities are mediated through the stabilization of p53 or in a p53-independent manner. Introducing a point mutation (L46D) into the conserved hydrophobic domain (37-51) in p19Arf annulled ARF/CtBP2 interaction and mediated cell survival by rendering cells irresponsive to apoptosis. In vivo analysis on the percentage of lymphoma free survivals in ARFL46D/L46D mice indicated that disrupting ARF/CtBP2 binding resulted in a tumor spectrum similar to that in ARF-null mice. In this study, we characterized the functions of the hydrophobic domain of ARF in MEF cells under genotoxic stress, ultra-violet irradiation and oncogene activation. We demonstrated that cells bearing the mutation showed decreased responsiveness to H-RasV12 induced senescence consistent with p21 deficiency. We speculate that the deficit in p21 expression is possibly caused by CtBP2 repressive and oncogene -like properties.","abstract_has_math":false,"creators":["Hariz, Aymen"],"institution":null,"degree_name":"Master of Science","degree_level":"Thesis","degree_discipline":"Hematology, Oncology and Palliative Care","degree_department":null,"school":null,"contributors":["Steven Grossman"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-04-25T07:00:00Z","date_published":"2013-04-25T07:00:00Z","updated_at":"2026-07-24T05:53:56Z","subjects":["Defense"],"languages":[],"rights":["© The Author"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarscompass.vcu.edu/etd/481"],"render_values":[{"text":"https://scholarscompass.vcu.edu/etd/481","href":"https://scholarscompass.vcu.edu/etd/481","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.25772/ZVNG-WR42","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Steven Grossman"]},{"key":"dc:creator","label":"Author","values":["Hariz, Aymen"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2018-05-13T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Hematology, Oncology and Palliative Care"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Defense"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["© The Author"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.25772/ZVNG-WR42","https://scholarscompass.vcu.edu/etd/481"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The INK4A-ARF locus encodes two tumor suppressors; p16 and p19Arf, both of which restrain cell growth by regulating the functions of Retinoblastoma (Rb) and p53 respectively. Throughout development, p19Arf is kept at minimal levels, but under conditions of oncogenic stress, p19Arf expression is induced and its tumor suppressive activities are mediated through the stabilization of p53 or in a p53-independent manner. Introducing a point mutation (L46D) into the conserved hydrophobic domain (37-51) in p19Arf annulled ARF/CtBP2 interaction and mediated cell survival by rendering cells irresponsive to apoptosis. In vivo analysis on the percentage of lymphoma free survivals in ARFL46D/L46D mice indicated that disrupting ARF/CtBP2 binding resulted in a tumor spectrum similar to that in ARF-null mice. In this study, we characterized the functions of the hydrophobic domain of ARF in MEF cells under genotoxic stress, ultra-violet irradiation and oncogene activation. We demonstrated that cells bearing the mutation showed decreased responsiveness to H-RasV12 induced senescence consistent with p21 deficiency. We speculate that the deficit in p21 expression is possibly caused by CtBP2 repressive and oncogene -like properties."]},{"key":"dc:title","label":"Title","values":["Defining the functions of a conserved hydrophobic domain in the ARF tumor suppressor"]}]}],"canonical_facts":{"dc:contributor":["Steven Grossman"],"dc:creator":["Hariz, Aymen"],"dc:date.available":["2018-05-13T07:00:00Z"],"dc:description.abstract":["The INK4A-ARF locus encodes two tumor suppressors; p16 and p19Arf, both of which restrain cell growth by regulating the functions of Retinoblastoma (Rb) and p53 respectively. Throughout development, p19Arf is kept at minimal levels, but under conditions of oncogenic stress, p19Arf expression is induced and its tumor suppressive activities are mediated through the stabilization of p53 or in a p53-independent manner. Introducing a point mutation (L46D) into the conserved hydrophobic domain (37-51) in p19Arf annulled ARF/CtBP2 interaction and mediated cell survival by rendering cells irresponsive to apoptosis. In vivo analysis on the percentage of lymphoma free survivals in ARFL46D/L46D mice indicated that disrupting ARF/CtBP2 binding resulted in a tumor spectrum similar to that in ARF-null mice. In this study, we characterized the functions of the hydrophobic domain of ARF in MEF cells under genotoxic stress, ultra-violet irradiation and oncogene activation. We demonstrated that cells bearing the mutation showed decreased responsiveness to H-RasV12 induced senescence consistent with p21 deficiency. We speculate that the deficit in p21 expression is possibly caused by CtBP2 repressive and oncogene -like properties."],"dc:identifier":["https://doi.org/10.25772/ZVNG-WR42","https://scholarscompass.vcu.edu/etd/481"],"dc:rights":["© The Author"],"dc:subject":["Defense"],"dc:title":["Defining the functions of a conserved hydrophobic domain in the ARF tumor suppressor"],"thesis:degree_discipline":["Hematology, Oncology and Palliative Care"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science"]},"updated_at":"2026-07-24T05:53:56Z"}