The exploration of magnetism in two-dimensional layered materials has attracted extensive research interest.For the monoclinic phase Crl_(3) with interlayer antiferromagnetism,finding a static and robust way of realizing the intrinsic interlayer ferromagnetic coupling is desirable.In this work,we study the electronic structure and magnetic properties of the nonmag-netic element(e.g.,O,S,Se,N,P,As,and C)doped bi-and triple-layer Crl_(3) systems via first-principles calculations.Our results demonstrate that O,P,S,As,and Se doped Crls bilayer can realize interlayer ferromagnetism.Further analysis shows that the interlayer ferromagnetic coupling in the doped few-layer Crls is closely related to the formation of localized spin-polarized state around the doped elements.Further study presents that,for As-doped tri-layer Crl_(3),it can realize interlayer ferromagnetic coupling.This work proves that nonmagnetic element doping can realize the interlayer ferromagnetically-coupled few-layer Crl_(3) while maintaining its semiconducting characteristics without introducing additional carriers.
The ubiquitin–proteasome system and the autophagy system are the two primary mechanisms used by eukaryotes to maintain protein homeostasis,and both are closely related to the pathogenicity of the rice blast fungus.In this research,we identified MoCand2 as an inhibitor of ubiquitination in Magnaporthe oryzae.Through this role,MoCand2 participates in the regulation of autophagy and pathogenicity.Spe-cifically,we found that deletion of MoCand2 increased the ubiquitination level in M.oryzae,whereas overexpression of MoCand2 inhibited the accumulation of ubiquitinated proteins.Interaction analyses showed that MoCand2 is a subunit of Cullin-RING ligases(CRLs).It suppresses ubiquitination by blocking the assembly of CRLs and downregulating the expression of key CRL subunits.Further research indi-cated that MoCand2 regulates autophagy through ubiquitination.MoCand2 knockout led to over-ubiquitination and over-degradation of MoTor,and we confirmed that MoTor content was negatively correlated with autophagy level.In addition,MoCand2 knockout accelerated the K63 ubiquitination of MoAtg6 and strengthened the assembly and activity of the phosphatidylinositol-3-kinase class 3 complex,thus enhancing autophagy.Abnormal ubiquitination and autophagy in DMocand2 resulted in defects in growth,conidiation,stress resistance,and pathogenicity.Finally,sequence alignment and functional an-alyses in other phytopathogenic fungi confirmed the high conservation of fungal Cand2s.Our research thus reveals a novel mechanism by which ubiquitination regulates autophagy and pathogenicity in phyto-pathogenic fungi.
Yunran ZhangYunyun WeiMinghua WuMengyu LiuShuang LiangXueming ZhuXiaohong LiuFucheng Lin
Cullin-RING E3 ubiquitin ligases(CRLs),the largest family of multi-subunit E3 ubiquitin ligases in eukaryotic cells,represent core cellular machinery for executing protein degradation and maintaining proteostasis.Here,we asked what roles Cullin proteins play in human mesenchymal stem cell(hMSC)homeostasis and senescence.To this end,we conducted a comparative aging phenotype analysis by individually knocking down Cullin members in three senescence models:replicative senescent hMSCs,Hutchinson-Gilford Progeria Syndrome hMSCs,and Werner syndrome hMSCs.Among all family members,we found that CUL2 deficiency rendered hMSCs the most susceptible to senescence.To investigate CUL2-specific underlying mechanisms,we then applied CRISPR/Cas9-mediated gene editing technology to generate CUL2-deficient human embryonic stem cells(hESCs).When we differentiated these into h MSCs,we found that CUL2 deletion markedly accelerates hMSC senescence.Importantly,we identified that CUL2 targets and promotes ubiquitin proteasome-mediated degradation of TSPYL2(a known negative regulator of proliferation)through the substrate receptor protein APPBP2,which in turn downregulates one of the canonical aging marker-P21^(waf1/cip1),and thereby delays senescence.Our work provides important insights into how CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts hMSC senescence,providing a molecular basis for directing intervention strategies against aging and aging-related diseases.
Tumorigenesis hinges on the reprogramming of cellular metabolisms to meet the requirements of intracellular biomass,characterized by the acquisition of nutrients from the environment as a common feature(Pavlova and Thompson,2016).Moreover,to fine-tune and support the cellular activities essential for growth and survival,tumor cells integrate multiple metabolic pathways to regulate nutrient availability upon metabolic reprogramming in tumor microenvironment(Lobel et al.,2023).Glutamine is one of the principal nutrients and the most abundant plasma amino acids,and cancer cells are highly dependent on it for proliferation(Yang et al.,2017).Cancer cells uptake glutamine through its transporters and use it as both nitrogen and carbon sources for biosynthetic processes and anabolic metabolites.During the glutaminolysis,glutamine intermediate glutamate can be metabolically converted intoα-ketoglutarate(α-KG)and then it enters into the tricarboxylic acid(TCA)cycle,or be utilized to produce glutathione(Lobel et al.,2023).
