Presentation Title (IN ALL CAPS)

HIV-1 NEF AND UB3EA- MEDIATED DEGREDATION OF p53

Presenter/Author(s) Information

Ginika ObiFollow

Departmental Affiliation and City, State, Zip for All Authors

UNT Health Science Center at Fort Worth, TX 76107

Scientific Abstract

Background: HIV-1 infection accelerates development of cancer, enhancing the frequency of cancers by 2-100 fold among HIV patients. However, the molecular mechanism for this process is still unclear. p53 is one of the most important cancer suppressors, being able to arrest cell growth and to induce apoptosis. HIV-1 Nef, an essential protein for viral pathogenesis, is known to transfer to even non-susceptible cells by HIV infection, like tumor cells, and to dysregulate cell physiology in the target cells by interacting with p53, suggesting that Nef could be a critical modulator in the process of cancer progression. Purpose: We hypothesize that the transferred Nef could contribute to the observed acceleration of cancer progression by suppressing p53 activity. Methods: Western blot analysis was performed to investigate stability of endogenous as well as exogenous p53, Nef and UB3EA. Subcellular localization was examined by immunofluorescence microscopy. Results: The level of endogenous p53 was significantly reduced by the expression of Nef protein in a dose dependent manner. Similarly, Nef was degraded by expression of exogenous p53, indicating that the degradation of the proteins is reciprocal. p53 and UB3EA mutually degrade each other. In supporting of these observations, p53 was detected in both cytoplasm and nucleus, and Nef was co-localized with the cytoplasmic p53. Conclusion: Nef and UB3EA could play a pivotal role in expedition of the progression of cancer by manipulating the stability of p53 which has a cardinal function in tumor suppression. Keywords: p53, HIV-1 Nef, UB3EA, Protein Degradation

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HIV-1 NEF AND UB3EA- MEDIATED DEGREDATION OF p53

Background: HIV-1 infection accelerates development of cancer, enhancing the frequency of cancers by 2-100 fold among HIV patients. However, the molecular mechanism for this process is still unclear. p53 is one of the most important cancer suppressors, being able to arrest cell growth and to induce apoptosis. HIV-1 Nef, an essential protein for viral pathogenesis, is known to transfer to even non-susceptible cells by HIV infection, like tumor cells, and to dysregulate cell physiology in the target cells by interacting with p53, suggesting that Nef could be a critical modulator in the process of cancer progression. Purpose: We hypothesize that the transferred Nef could contribute to the observed acceleration of cancer progression by suppressing p53 activity. Methods: Western blot analysis was performed to investigate stability of endogenous as well as exogenous p53, Nef and UB3EA. Subcellular localization was examined by immunofluorescence microscopy. Results: The level of endogenous p53 was significantly reduced by the expression of Nef protein in a dose dependent manner. Similarly, Nef was degraded by expression of exogenous p53, indicating that the degradation of the proteins is reciprocal. p53 and UB3EA mutually degrade each other. In supporting of these observations, p53 was detected in both cytoplasm and nucleus, and Nef was co-localized with the cytoplasmic p53. Conclusion: Nef and UB3EA could play a pivotal role in expedition of the progression of cancer by manipulating the stability of p53 which has a cardinal function in tumor suppression. Keywords: p53, HIV-1 Nef, UB3EA, Protein Degradation

Manuscript Number

1048