Growth factor deprivation induces cytosolic translocation of SIRT1

摘要

Sirtuin type 1 (SIRT1); a NAD+-dependent histone deacetylases; plays a critical role in cellular senescence; aging and longevity. In general; SIRT1 is localized in nucleus and is believed as a nuclear protein. Though overexpression of SIRT1 delays senescence; SIRT1 -protein levels decline naturally in thymus and heart during aging. In the present studies; we investigated the subcellular localization of SIRT1 in response to growth factor deprivation in African green monkey SV40-transformed kidney fibroblast cells (COS-7). Using SIRT1-EGFP fluorescence reporter; we found that SIRT1 localized to nucleus in physiological conditions. We devised a model enabling cell senescence via growth factor deprivation; and we found that SIRT1 partially translocated to cytosol under the treatment; suggesting a reduced level of SIRTl's activity. We found PDK/Akt pathway was involved in the inhibition of SIRTl's cytosolic translocation; because inhibition of these kinases significantly decreased the amount of SIRT1 maintained in nucleus. Taken together; we demonstrated that growth factor deprivation induces cytosolic translocation of SIRT1; which suggesting a possible connection between cytoplasm-localized SIRT1 and the aging process.