Downregulation of SNRPG induces cell cycle arrest and sensitizes human glioblastoma cells to temozolomide by targeting Myc through a p53-dependent signaling pathway

Objective:Temozolomide(TMZ)is commonly used for glioblastoma multiforme(GBM)chemotherapy.However,drug resistance limits its therapeutic effect in GBM treatment.RNA-binding proteins(RBPs)have vital roles in posttranscriptional events.While disturbance of RBP-RNA network activity is potentially associated with cancer development,the precise mechanisms are not fully known.The SNRPG gene,encoding small nuclear ribonucleoprotein polypeptide G,was recently found to be related to cancer incidence,but its exact function has yet to be elucidated.Methods:SNRPG knockdown was achieved via short hairpin RNAs.Gene expression profiling and Western blot analyses were used to identify potential glioma cell growth signaling pathways affected by SNRPG.Xenograft tumors were examined to determine the carcinogenic effects of SNRPG on glioma tissues.Results:The SNRPG-mediated inhibitory effect on glioma cells might be due to the targeted prevention of Myc and p53.In addition,the effects of SNRPG loss on p53 levels and cell cycle progression were found to be Myc-dependent.Furthermore,SNRPG was increased in TMZ-resistant GBM cells,and downregulation of SNRPG potentially sensitized resistant cells to TMZ,suggesting that SNRPG deficiency decreases the chemoresistance of GBM cells to TMZ via the p53 signaling pathway.Our data confirmed that SNRPG suppression sensitizes GBM cells to TMZ by targeting Myc via the p53 signaling cascade.Conclusions:These results indicated that SNRPG is a probable molecular target of GBM and suggested that suppressing SNRPG in resistant GBM cells might be a substantially beneficial method for overcoming essential drug resistance.

Quantitative proteomics reveals redox-based functional regulation of photosynthesis under fluctuating light in plants

Photosynthesis involves a series of redox reactions and is the major source of reactive oxygen species in plant cells.Fluctuating light(FL) levels,which occur commonly in natural environments,affect photosynthesis;however,little is known about the specific effects of FL on the redox regulation of photosynthesis.Here,we performed global quantitative mapping of the Arabidopsis thaliana cysteine thiol redox proteome under constant light and FL conditions.We identified8857 redox-switched thiols in 4350 proteins,and1501 proteins that are differentially modified depending on light conditions.Notably,proteins related to photosynthesis,especially photosystem I(PSI),are operational thiol-switching hotspots.Exposure of wild-type A.thaliana to FL resulted in decreased PSI abundance,stability,and activity.Interestingly,in response to PSI photodamage,more of the PSI assembly factor PSA3 dynamically switches to the reduced state.Furthermore,the Cys199 and Cys200 sites in PSA3 are necessary for its full function.Moreover,thioredoxin m(Trx m) proteins play roles in redox switching of PSA3,and are required for PSI activity and photosynthesis.This study thus reveals a mechanism for redox-based regulation of PSI under FL,and provides insight into the dynamic acclimation of photosynthesis in a changing environment.