Talks
Presentation Type
Oral Presentation
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background: CARF (Collaborator of ARF)/CDKN2AIP is an essential protein, first cloned as a binding partner of ARF. It was subsequently shown to interact with p53, HDM2 proteins and regulate growth arrest and apoptosis by its multimodal mechanism of action. Over-expression of CARF caused senescence like growth arrest of cells, its knock-down triggered apoptosis. Intriguingly, malignantly transformed cells showed high level of CARF expression. Based on these findings, we hypothesized that level of CARF expression may be a key determinant of cell proliferation fates; where an increase in its levels causes growth arrest/senescence, but beyond a threshold it activates carcinogenesis.
Methods: We utilized in vitro cell culture models using retrovirus-driven expression of CARF to achieve over-expression and super-expression of CARF. Analysis of CARF levels was undertaken by biochemical and imaging protocols. Cells exposed to a variety of stresses including physiological, environmental, oxidative, radiation and chemotherapeutics was examined for CARF expression and corresponding cell proliferation fates.
Results: Induction of Senescence was seen in cells over-expressing CARF. On the other hand, cells compromised for CARF showed apoptosis, and the ones with super-expression of CARF exhibited malignant transformation. CARF expression analysis in these experimental models endorsed the concept of cell-fate determining role of CARF.
Conclusions: We present molecular evidence of the bridging role of CARF in stress-aging-cancer phenotypes and its application in pharmaceuticals and nutraceuticals as a diagnostic and prognostic marker for stress and cancer treatments.
Academic/Professional Position
Graduate Student
Recommended Citation
Khurana, Mallika; Kalra, Rajkumar Singh; Chaudhary, Anupama; Omar, Amr; Li, Xiaoshuai; Kaul, Sunil C.; and Wadhwa, Renu, "Stress-induced changes in CARF expression determine growth arrest, apoptosis, or malignant transformation in cultured human cells: Molecular evidence and its application" (2023). Research Symposium. 43.
https://scholarworks.utrgv.edu/somrs/theme1/track1/43
Included in
Alternative and Complementary Medicine Commons, Other Pharmacy and Pharmaceutical Sciences Commons
Stress-induced changes in CARF expression determine growth arrest, apoptosis, or malignant transformation in cultured human cells: Molecular evidence and its application
Background: CARF (Collaborator of ARF)/CDKN2AIP is an essential protein, first cloned as a binding partner of ARF. It was subsequently shown to interact with p53, HDM2 proteins and regulate growth arrest and apoptosis by its multimodal mechanism of action. Over-expression of CARF caused senescence like growth arrest of cells, its knock-down triggered apoptosis. Intriguingly, malignantly transformed cells showed high level of CARF expression. Based on these findings, we hypothesized that level of CARF expression may be a key determinant of cell proliferation fates; where an increase in its levels causes growth arrest/senescence, but beyond a threshold it activates carcinogenesis.
Methods: We utilized in vitro cell culture models using retrovirus-driven expression of CARF to achieve over-expression and super-expression of CARF. Analysis of CARF levels was undertaken by biochemical and imaging protocols. Cells exposed to a variety of stresses including physiological, environmental, oxidative, radiation and chemotherapeutics was examined for CARF expression and corresponding cell proliferation fates.
Results: Induction of Senescence was seen in cells over-expressing CARF. On the other hand, cells compromised for CARF showed apoptosis, and the ones with super-expression of CARF exhibited malignant transformation. CARF expression analysis in these experimental models endorsed the concept of cell-fate determining role of CARF.
Conclusions: We present molecular evidence of the bridging role of CARF in stress-aging-cancer phenotypes and its application in pharmaceuticals and nutraceuticals as a diagnostic and prognostic marker for stress and cancer treatments.