The ubiquitin codes in cellular stress responses

Ubiquitination/ubiquitylation,one of the most fundamental post-translational modifications,regulates almost every critical cellular process in eukaryotes.Emerging evidence has shown that essential components of numerous biological processes undergo ubiquitination in mammalian cells upon exposure to diverse stresses,from exogenous factors to cellular reactions,causing a dazzling variety of functional consequences.Various forms of ubiquitin sig-nals generated by ubiquitylation events in specific milieus,known as ubiquitin codes,constitute an intrinsic part of myriad cellular stress responses.These ubiquitination events,leading to proteolytic turnover of the substrates or just switch in functionality,initiate,regulate,or supervise multiple cellular stress-associated responses,supporting adaptation,homeostasis recovery,and survival of the stressed cells.In this review,we attempted to summarize the crucial roles of ubiquitination in response to different environmental and intracellular stresses,while discussing how stresses modulate the ubiquitin system.This review also updates the most recent advances in understanding ubiquitination machinery as well as different stress responses and discusses some important questions that may warrant future investigation.

Host cyclophilin A facilitates SARS-CoV-2 infection by binding and stabilizing spike on virions

Dear Editor,The novel coronavirus SARS-CoV-2 rapidly evolutes to increase its infectivity and transmissibility,facilitates its immune escape,impairs vaccine efficacy,and currently causes repeated infections in human,which is mainly determined by the accumulated mutations in spike(S).1 Transmembrane S is a heavily glycosylated protein on the surface of the virion as homotrimer,responsible for binding to human angiotensin-converting enzyme 2(hACE2)receptor.2 While the architecture of S trimers has been well studied,how the stability of S is regulated by potential host factors remains unknown.

Non-proteolytic ubiquitination of HBx controls HBV replication

Dear Editor,Although effective vaccines and antiviral therapies are available,hepatitis B virus(HBV)infection is still a serious global health threat.Persistent HBV infection remains the principal cause of liver cirrhosis and hepatocellular carcinoma(HCC).HBV is a small DNA virus,owning a~3.2 kb genome that encodes several proteins:viral DNA polymerase,core antigen(HBcAg),E antigen(HBeAg),three surface antigens(PreS1/PreS2/HBsAg),and a regulatory X protein(HBx)(Lamontagne et al.,2016).X protein,named for its lack of homology with any known proteins,is a 154 aa protein that plays an essential role in HBV biology and regulates the development of HCC(Yang et al.,2022).Although previous studies have strongly expanded our understanding of HBx,the regulation of HBx is not completely elucidated.

Enterohemorrhagic E.coli effector NleL disrupts host NF-κB signaling by targeting multiple host proteins

Dear Editor,Enterohemorrhagic Escherichia coli(EHEC)0157:H7,a major diarrheagenic pathogen,can cause bloody diarrhea,hemorrhagic colitis,and>90%of hemolytic uremic syndrome in humans(Mead and Griffin,1998).Many previous studies have demonstrated that 0157:H7 could disrupt host ubiquitin(Ub)system by delivering virulence effectors into host cells with the type III secretion system(T3SS).NleL(also named EspX7)emerged as one of such effectors,whose E3-like activity was first identified in vitro in 2011(Lin et al.,2011).