| Enterovirus 71(EV71)is a single-stranded positive-sense RNA virus of the Picornaviridae family.EV71 is the main pathogen causing hand-foot-mouth disease(HFMD)in infants and children,which can also lead to severe neurological diseases and even death.Therefore,understanding the replication mechanism of EV71 is of great significance for the prevention and control of EV71 induced diseases.Beclin1(BECN1,a mammalian homologue of ATG6 in yeast)is an important core protein for the initiation and normal process of autophagy in cells.In addition to its involvement in autophagy,Beclin1 has also been reported to play an important role in cancer and innate immune signaling pathways.However,there are few reports on what a character Beclin1 plays in EV71 replication and how EV71 influences the function of Beclin1.Here,we primarily found that Beclin1 facilitates EV71 replication in RD(human rhabdomyosarcoma cells)and U251 cells(human glioma cells)from time gradients and concentration gradients,and autophagy was actually induced but Beclin1 was not significantly affected at either m RNA level or protein level during early EV71 infection(0-12h).Further studies discovered that Beclin1 could interacts with EV71 non-structural protein 3D and thus promoted the replication of EV71.Collectively,we found a new function of Beclin1 in viral infection and revealed a new host factors-mediated regulating mechanism to promote EV71 replication,thus providing a potential therapeutic target for the prevention and control of EV71-induced diseases.ASB17 is a member of the ASB family with a total of 18 members.The common structural feature of ASB family is that each member contains a SOCS box at C-terminal,and a varying number of Ankyrin repeat domains at N-terminal.Apoptosis is the spontaneous and orderly death of cells controlled by its own genes,and it is a complex and orderly regulation process of gene expression,which has important physiological significance for the normal growth and development of the body and the elimination of senescent and diseased cells.In this study,ASB17 was found to interact with BCL2,BCLX,BCLW and MCL1 in the BCL2 family,which regulates apoptosis.Subsequently,we found that ASB17 can promote apoptosis and depend on caspase family conduction.In the mechanism study,it was further recognized that ASB17 can specifically degrade MCL1 and BCLW by an ubiquitination-dependent manner,and both proteins belong to the family of apoptosis inhibitors,so ASB17 is able to accelerate apoptosis.In short,we have identified a new function of ASB17 to promote apoptosis,and have tentatively elucidated a possible mechanism.In addition,MCL1 and BCLW are abnormally highly expressed in some cancer cells,which causes the apoptosis of cancer cells to be obstructed.Therefore,we also provide possible effective strategies for cancer treatment programs targeting MCL1. |
