Sir2alpha-mediated regulation of p53 function, a new target for cancer therapy
Lead Inventors: Wei Gu Ph.D.; JianYuan Luo Ph.D.Problem or Unmet Need:The p53 tumor suppressor exerts anti-proliferative effects, including growth arrest, apoptosis and cell senescence in response to various types of stress. Inactivation of p53 functions has been well documented as a common mechanism for tumorigenesis. Many cancer therapy drugs have been designed based on either reactivating p53 functions or inactivating p53 negative regulators. But the precise mechanism by which p53 is activated is not completely understood, which limit the development of more efficient cancer therapy drugs. The technology identified that Sir2alpha interacts with p53 and attenuates p53-mediated functions, such as p53-dependent apoptosis in response to DNA damage and oxidative stress. Thereby, based on this Sir2alpha-mediated regulation of p53 function, the technology provides a method to modulate the sensitivity of cells in p53-dependent apoptotic response, which could be used as new molecular target for cancer therapy.
The technology provides a method to precisely control p53 activities The technology identified a novel p53 regulation pathway, combining this pathway with other anti-cancer drug based on DNA damage and HDAC-mediated deacetylase inhibition may have synergistic effects in cancer therapy for maximally activating p53
The technology can be used as a therapeutic strategy, treating or inhibiting cancer by administering a therapeutically effective amount of an agent that inhibits the ability of Sir2alpha to inhibit p53-dependent apoptosis. For example, nicotinamide (Vitamin B3) can inhibit the NAD-dependent p53 inactivation induced by Sir2alpha, therefore enhance the p53 tumor suppressive activity in vivo. The technology can be used as a strategy to prolong the life span of a subject, decrease the stress induced damage to a subject's cells, by administering agent that increases the ability of Sir2alpha to inhibit p53-dependent apoptosis.
The technology identified that Sir2alpha interacts with p53 and attenuates p53-mediated functions, such as p53-dependent apoptosis in response to DNA damage and oxidative stress. Thereby, based on this Sir2alpha-mediated regulation of p53 function, t...
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