Effect Of Ubiquitin-like Protein UFM1 On Cell Senescence

UFM1?the ubiquitin-fold modifier 1?is an ubiquitin-like protein discovered more than a decade ago,whose structure is similar to ubiquitin.Consistent with ubiquitination,UFM1 undergoes a cascade of three-step enzymatic reactions with target proteins,including E1,UFM1-activating enzymatic 5?UBA5?;E2,UFM1-conjugatin enzymatic 1?UFC1?;E3,UFM1-specific ligase 1?UFL1?.Cell senescence is a complex and heterogeneous process,also is a stable form of cell cycle arrest that limits the proliferation potential of cells.Senescence is occurred after a period of cell proliferation or occurred more rapidly in respond to acute stress.Once a cell enters into cell senescence,it no longer divides,and the morphology and metabolism of the cell undergoes tremendous changes.Cell senescence plays a crucial role in tumor inhibition and aging.According to reports in the literatures,the UFM1 cascade is associated with a variety of human diseases,many of which are aging-related disease.We hypothesize that UFM1 functions in cell senescence regulation.We have established replicable senescent cell models,H₂O₂ and X-ray induced senescent cell models.We found that UFM1 is upregulated in replicative senescent cells.At the same time,the same upregulation was also observed in premature senescent cells treated with H₂O₂ and X-ray.We have prepared the UFM1 shRNAs lentivirus for further study of the specific role of UFM1 in cell senescence.Our results indicate that the expression of knockdown UFM1 induces cells entered into cell senescence.This result suggests that UFM1 is indeed involved in the process of cell senescence,knockdown UFM1induced cell senescence may be associated with endoplasmic reticulum stress and oxidative stress,although the underlining mechanism needs further investigation.We believe that UFM1 modification may have important implications in aging-related disease.Currently only ASC1 and DDRGK1 have been reported as the target protein of UFM1.We believe that there are more substrate proteins with critical functions through the modification of UFM1 in cells.Study on the function and the regulation of UFM1 modification would provide insights into our understanding of molecular mechanisms of aging and aging-associated diseases...