Angiogenesis,the expansion of preexisting blood vessels,is a complex process required for tumor growth and metastasis.Although current antiangiogenic strategies have shown promising results in several cancer types,identification of additional antiangiogenic targets is required to improve the therapeutic response.Herein,we show that the microtubule-binding protein CLIP-170(cytoplasmic linker protein of 170 kDa)is highly expressed in breast tumor samples and correlates positively with blood vessel density.Depletion of CLIP-170 signifi cantly impaired vascular endothelial tube formation and sprouting in vitro and inhibited breast tumor growth in mice by decreasing tumor vascularization.Our data further show that CLIP-170 is important for the migration but not the proliferation of vascular endothelial cells.In addition,CLIP-170 promotes the polarization of endothelial cells in response to the angiogenic stimulus.These fi ndings thus demonstrate a critical role for CLIP-170 in tumor angiogenesis and suggest its potential as a novel antiangiogenic target.
The atrazine chlorohydroiase(AtzA) attracts widespread interests as it catalyzes the toxic atrazine to non-tox...
Yi-Cun Wang1,Xiao-Long Li1,Hai-Wei Chen(1,2),Xi-Wen Chen(1),De-Fu Chen(1) 1 Laboratory of Molecular Genetics,College of Life Sciences,Nankai University,Tianjin,China,2 College of Life Sciences,Chifeng College,Chifeng,China
Based on the amyloid hypothesis,anti-β-amyloid(Aβ)therapy has dominated clinical trials for the prevention and treatment of Alzheimer’s disease(AD)in recent years.A key element of this strategy is the interaction between therapeutic agents and Aβ.However,the design and development of artificial receptors that may render selective and strong recognition toward Aβremains a huge challenge because of the complexity and size of peptide guests and their flexible conformation.
Viral protein R(Vpr) plays an important role in the replication and pathogenesis of Human immunodeficiency virus type 1(HIV-1). Some of the various functions attributed to Vpr, including the induction of G2/M cell cycle arrest, activating the NF-κB pathway, and promoting viral reverse transcription, might be interrelated. To test this hypothesis, a panel of Vpr mutants were investigated for their ability to induce G2/M arrest and to activate the NF-κB pathway. The results showed that the Vpr mutants that failed to activate NF-κB also lost the activity to induce G2/M arrest, which suggests that inducing G2/M arrest via Vpr depends at least partially on the activation of NF-κB. This latter possibility is supported by data showing that knocking down the key factors in the NF-κB pathway – p65, Rel B, IKKα, or IKKβ– partially rescued the G2/M arrest induced by Vpr.Our results suggest that the NF-κB pathway is probably involved in Vpr-induced G2/M cell cycle arrest.
Non-coding RNAs(nc RNAs),such as micro RNAs and large intergenic non-coding RNAs,have been shown to play essential roles in regulating pluripotency.Yet,it is not clear the role of natural antisense transcripts(NATs),also belonging to nc RNAs,in embryonic stem cells.However,the role of NATs in embryonic stem cells remains unknown.We further confirmed the expression of the NATs of three key pluripotency genes,Oct4,Nanog and Sox2.Moreover,overexpression of Sox2-NAT reduces the expression of Sox2 protein,and slightly enhances the Sox2 m RNA level.Altogether,our data indicated that like other nc RNAs,NATs might be involved in pluripotency maintenance.
Expression of recombinant protein in Escherichia coli (E.coli) is generally considered as one of the ideal systems to produce proteins for industrial production.However,the majority of proteins usually fail to fold into their native state and accumulate as insoluble inclusion bodies with no bio- logical activity in E.coli(Yang et al.,2003).
Bovine foamy virus(BFV) is a complex retrovirus that infects cattle. Like all retroviruses, BFV encodes a transactivator Tas protein(BTas) that increases gene transcription from viral promoters.BFV encodes two promoters that can interact with BTas, a conserved promoter in the 5' long terminal repeat(LTR) and a unique internal promoter(IP). Our previous study showed that BTas is acetylated by p300 at residues K66, K109, and K110, which markedly enhanced the ability of BTas to bind to DNA. However, whether these residues are important for BFV replication was not determined. Therefore, in this study we provide direct evidence that BTas is required for BFV replication and demonstrate that residues K66, K109, and K110 are critical for BTas function and BFV replication. Full-length infectious clones were generated, which were BTas deficient or contained lysine to arginine(K→R) mutations at position 66, 109, and/or 110. In vivo data indicated that K→R mutations at positions 66, 109, and 110 in BTas impaired transactivation of both the LTR and IP promoters. In addition, the K→R mutations in full-length infectious clones reduced expression of viral proteins, and the triple mutant and BTas deletion completely abrogated viral replication. Taken together, these results indicate that lysine residues at positions 66, 109, and 110 in the BTas protein are crucial for BFV replication and suggest a potential role for BTas acetylation in regulating the viral life cycle.
Suzhen ZhangXiaoxu CuiJing LiZhibin LiangWentao QiaoJuan Tan
