Novel Role of PAPSS2 as a Senescence Regulatory Protein

초록

Although great progress has been made in cellular senescence during the last decade, further elucidation of senescence-regulatory molecules and their activation mechanisms will improve our understanding regarding the physiological significance of cellular senescence. The heparan sulfate (HS) sulfation is an important post-translational modification that plays a regulatory role in cell growth, motility, and metabolism. However, relationship between HS sulfation and cellular senescence has not been determined yet. Thus, to know the role of HS sulfation status in cellular senescence, we depleted PAPSS2, a synthetic enzyme of the sulfur donor PAPS. We found cellular senescence through FGFR/AKT signaling pathway in PAPSS2 depleted MCF7 human breast carcinoma cells and human diploid fibroblast (HDF) cells. p53 and p21 accumulation was essential for PAPSS2-mediated cellular senescence. And, we also detected a decrease in sulfated HS on the cell surface during the replicative senescence of HDFs. These results indicate that HS sulfation status is tightly linked to premature and replicative senescence. Collectively, our results suggest a new role of PAPSS2 in cellular senescence via regulation of HS sulfation.