AstraZeneca公司合作研究癌症“分子伴侣”

未来三年内，AstraZeneca公司将投入4百万英镑，与两个合作伙伴共同开展一个肿瘤研究项目。 欧洲领先的肿瘤研究中心，癌症研究学会（ICR）和癌症研究技术（CRT）——英国癌症研究基金会附属机构，将与公司合作寻找新的抗癌药物，目标为分子伴侣。

热休克蛋白生物学功能及其在肾损伤中作用的研究进展

热休克蛋白（heat shock protein，HSP）又称应激蛋白，是生物体内或离体细胞产生的一组特殊的蛋白，目前已发现10多种，HSP是一类在进化上高度保守，广泛存在于原核和真核生物细胞内的一种蛋白质。其基本功能为帮助新生蛋白质的正确折叠、移位、维持和受损蛋白质的修复、移除、降解，被人们形象的称之为“分子伴侣”。

AtFKBP53 is a histone chaperone required for repression of ribosomal RNA gene expression in Arabidopsis

Chromatin structure is important for controlling gene expression, but mechanisms underlying chromatin remodel- ing are not fully understood. Here we report that an FKBP （FK506 binding protein） type immunophilin, AtFKBP53, possesses histone chaperone activity and is required for repressing ribosomal gene expression in Arabidopsis. The At- FKBP53 protein is a multidomain FKBP with a typical peptidylprolyl isomerase （PPIase） domain and several highly charged domains. Using nucleosome assembly assays, we showed that AtFKBP53 has histone chaperone activity and the charged acidic domains are sufficient for the activity. We show that AtFKBP53 interacts with histone H3 through the acidic domains, whereas the PPIase domain is dispensable for histone chaperone activity or histone binding. Ri- bosomal RNA gene （18S rDNA） is overexpressed when AtFKBP53 activity is reduced or eliminated in Arabidopsis plants. Chromatin immunoprecipitation assay showed that AtFKBP53 is associated with the 18S rDNA gene chro- matin, implicating that AtFKBP53 represses rRNA genes at the chromatin level. This study identifies a new histone chaperone in plants that functions in chromatin remodeling and regulation of transcription.

The Life of a Protein Molecule——Protein Quality Control

The research progress in molecular chaperones, unfolded protein response （UPR） and ER-associated degradation （ERAD） involved in the protein quality control was summarized in this paper, and then the existing problems and the future devel- opment prospect were also discussed. It was pointed out that the life process of protein experienced four stages including synthesizing, folding, assembling and degradation, while each stage required strict quality control. In endoplasmic reticulum （ER）, a variety of proteins had been synthesized, folded and modified to form func- tional proteins with certain conformation. When the folding was blocked in ER, the unfolded proteins would aggregate and induce the UPR, which up-regulated the level of modification enzymes folded by a series of molecular chaperones and proteins to help them accomplish folding and assembling. If these proteins were still folded incorrectly, they would enter into ERAD for being degraded.

Molecular cloning and expression of a heat-shock cognate 70 (hsc70) gene from swordtail fish (Xiphophorus helleri)

Heat shock proteins are a family of molecular chaperones that are involved in many aspects of protein homeostasis. In the present study, a full-length cDNA, encoding the constitutively expressed 70-kDa heat shock cognate protein （Hsc70）, was isolated from swordtail fish （Xiphophorus helleri） and designated as XheHsc70. The Xhehsc70 cDNA was 2 104 bp long with an open reading frame of 1 941 bp, and it encoded a protein of 646 amino acids with a theoretical molecular weight of 70.77 kDa and an isoelectric point of 5.04. The deduced amino acid sequence shared 94.1%-98.6% identities with the Hsc70s from a number of other fish species. Tissue distribution results show that the Xhehsc70 mRNA was expressed in brain, heart, head kidney, kidney, spleen, liver, muscle, gill, and peripheral blood. After immunization with formalin-killed Vibrio alginolyticus cells there was a significant increase in the XhehscT0 mRNA transcriptional level in the head kidney of the vaccinated fish compared with in the control at 6, 12, 24, and 48 h as shown by quantitative real time RT-PCR. Based on an analysis of the amino acid sequence of XheHsc70, its phylogeny, and Xhehsc70 mRNA expression, XheHsc70 was identified as a member of the cytoplasmic Hsc70 （constitutive） subfamily of the Hsp70 family of heat shock proteins, suggesting that it may play a role in the immune response. The Xhehsc70 cDNA sequence reported in this study was submitted to GenBank under the accession number JF739182.

Single-step Purification of Molecular Chaperone GroEL by Expanded Bed Chromatography

Expanded bed adsorption (EBA) is an integrative downstream processing technique for the purification of biological substances directly from unclarified feedstock. In this study, molecular chaperone GroEL, an important protein folding helper both in vivo and in vitro, was purified by the single-step EBA technique from the unclarified homogenate of recombinant E. coli cells. Compared with packed bed adsorption, the EBA technique provided a single-step approach to yield an electrophoretic purity of GroEL. After the homogenate loading and column washing in the expanded bed mode, the GroEL protein was recovered by stepwise salt-gradient elution in packed-bed or expanded-bed modes, respectively. The expanded-bed elution mode was found as efficient as the packed-bed mode in the purification of GroEL from cell disruptate.

Expression of endoplasmic reticulum molecular chaperon GRP94 in human lung cancer tissues and its clinical significance

OBJECTIVE: To investigate the relationship between the expression of glucose regulated protein 94 (GRP94) at the level of mRNA and protein in vivo and in human lung cancer. METHODS: RT-PCR, immunohistochemistry and/or Western blot were used in 54 cases of lung cancer tissues and corresponding normal lung tissues. RESULTS: There was a significant overexpression of GRP94 mRNA and protein in lung cancer tissues as compared with lung normal tissues. In lung cancer tissue, the relative level of GRP94 mRNA as evaluated by RT-PCR was 3.48 +/- 2.06, the level of GRP94 protein as evaluated by immunohistochemistry was + + to + + +, and by Western blot was 256.7 +/- 80.6. In lung normal tissue, the relative level of GRP94 mRNA was 2.01 +/- 1.83, the level of GRP94 protein was + to + + and 108.1 +/- 42.3. The differences in expression of GRP94 between the two tissues were significant (P

Arabidopsis co-chaperonin CPN20 antagonizes Mg-chelatase H subunit to derepress ABA-responsive WRKY40 transcription repressor

Our previous study demonstrated that a chloroplast co-chaperonin 20(CPN20),one of the interaction partners of the magnesium-protoporphyrin IX chelatase H subunit(CHLH/ABAR),negatively regulates ABA signaling at the same node with ABAR but upstream of WRKY40 transcription repressor in Arabidopsis thaliana.In the present experiment,we showed that ABA directly inhibits the ABAR-CPN20 interaction,and also represses expression of CPN20,which depends on ABAR.CPN20 inhibits ABAR-WRKY40 interaction by competitively binding to ABAR.ABAR downregulates,but CPN20 upregulates,WRKY40 expression.The cpn20-1 mutation induces downregulation of WRKY40,and suppresses the upregulated level of WRKY40 due to the cch mutation in the ABAR gene.ABA-induced repressive effect of the WRKY40 gene is strengthened by downregulation of CPN20 but reduced by upregulation of CPN20.Together with our previously reported genetic data,we provide evidence that CPN20 functions through antagonizing the ABAR-WRKY40 coupled pathway,and ABA relieves this pathway of repression by inhibiting the ABAR-CPN20 interaction to activate ABAR-WRKY40 interaction.