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Highlights: [•] HAS2 may be a promising target for the radiosensitization of human cancer. [•] HAS2 is elevated (up to ∼10-fold) in irradiated radioresistant and -sensitive cancer cells. [•] HAS2 knockdown sensitizes cancer cells to radiation. [•] HAS2 knockdown potentiates irradiation-induced DNA damage and apoptotic death. [•] Thus, the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. [ABSTRACT FROM AUTHOR]

Abstract: Upon apoptotic stimulation, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a cytosolic enzyme normally active in glycolysis, translocates into the nucleus and activates an apoptotic cascade therein. In the present work, we show that SIRT1 prevents nuclear translocation of GAPDH via interaction with GAPDH. SIRT1 depletion triggered nuclear translocation of cytosolic GAPDH even in the absence of apoptotic stress. Such translocation was not, however, observed when SIRT1 enzymatic activity was inhibited, indicating that SIRT1 protein per se, rather than the deacetylase activity of the protein, is required to inhibit GAPDH translocation. Upon irradiation, SIRT1 prevented irradiation-induced nuclear translocation of GAPDH, accompanied by interaction of SIRT1 and GAPDH. Thus, SIRT1 functions to retain GAPDH in the cytosol, protecting the enzyme from nuclear translocation via interaction with these two proteins. This serves as a mechanism whereby SIRT1 regulates cell survival upon induction of apoptotic stress by means that include irradiation. [Copyright &y& Elsevier]

Highlights: [•] SIRT1 serves as an upstream negative regulator of β-TrCP. [•] SIRT1 depletion induces β-TrCP accumulation. [•] SIRT1 suppresses β-TrCP accumulation induced by resveratrol. [•] SIRT1 participates in promoting β-TrCP degradation. [•] SIRT1 suppression of β-TrCP synthesis occurs via post-translational degradation of the protein. [ABSTRACT FROM AUTHOR]