Phosphorylation regulates cullin-based ubiquitination in tumorigenesis

Cullin-RING ligases (CRLs) recognize and interact with substrates for ubiquitination and degradation, and can be targeted for disease treatment when the abnormal expression of substrates involves pathologic processes. Phosphorylation, either of substrates or receptors of CRLs, can alter their interaction. Phosphorylation-dependent ubiquitination and proteasome degradation influence various cellular processes and can contribute to the occurrence of various diseases, most often tumorigenesis. These processes have the potential to be used for tumor intervention through the regulation of the activities of related kinases, along with the regulation of the stability of specific oncoproteins and tumor suppressors. This review describes the mechanisms and biological functions of crosstalk between phosphorylation and ubiquitination, and most importantly its influence on tumorigenesis, to provide new directions and strategies for tumor therapy.

Apoptosis inhibition and chemosensitivities in GI carcinomas / 中华普通外科杂志

Objective To investigate the relationship between the expression of inhibition of apoptosis proteins like p53,survivin,bcl-2 and chemosensitivities in gastrointestinal tract carcinomas.Methods The expression of p53,survivin and bcl-2 were determined immunohjstochemically,and the chemosenisitivities to 9 drugs was measured by MTT assay in 84 tissue specimens of gastrointestinal carcinomas.Resuits Positive immunostainning for p53,survivin and bcl-2 were found in 64%,89%and 61%of cases.respectively.Correlation existed between the expression of Sllrvivin and bcl-2(r=0.3027,P＜0.05).In terms of relationship between expression of p53,survivin or bcl-2 and inhibition rates of tumor cells.the inhibition rates to PTX and DDP in p53 strong expression group were lower than those in weak group(t=2.1282,P:0.0363;t=3.8850,P=0.0002).When survivin expressed strongly,the inhibition rates for VCR and DDP decreased significantly(t=2.1693,P=0.0329;t=2.0247,P=0.0046),while that for OXA increased(t=-2.9070,P:0.0047).here were lower tumor inhibition rates for 5-FU.VCR,eADM and OXA in bcl-2 strong expression group than those in weak group(t=2.1483～3.2330,P=0.0347～0.0018,respectively).Conclusions The extent of the expression of P53.survivin or bcl-2 in gastrointestinal carcinomas was associated with the chemosensitivities of some drugs.In assessing the influence of p53,survivin or bcl-2 on durg resistance,many factors and mechanisms should be considered.

Relationship between the expressions of lectin-like oxidized low-density lipoprotein receptor-1 and apoptosis associated genes in placenta tissues and the pathogenesis of preeclampsia / 中华妇产科杂志

Objective To explore the expressions of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)and apoptosis related genes caspase-3,Bax and bcl-2 in placenta,and their associations with the pathogenesis of preeclampsia.Methods Thirty preeclampsia patients(preeclampsia group),hospitalized in Department of Obstetrics,Shengiing Hospital of China Medical University from June 2005 to December 2006,were selected as the subject group,and 40 normal pregnant women as control group.The expressions of LOX-1 and apoptosis related genes caspase-3.Bax and bel-2 in different gestational weeks'placenta tissues were examined using immunohistochemistry.RT-PCR and western-blot.Results (1)Immunohistochemical detection in preeclampsia group:at 20 w+1-24 w,24 w+1-28 w,28 w+1-32 w.32w+1-36 w+1-36 w+1-40 w,respectively,the results of LOX-1 were 20.1±1.8,25.6±1.3,32.8±1.6,34.3 ±1.5,39.9±1.2;in the control group they respectively were 11.2±0.6,18.5±1.6,26.1±1.8,28.3 4-1.6,32.3±1.6;the difierence was significant(P<0.05).In preeclampsia group,the results of easpase-3 were 12.3±0.9,16.3±0.9,24.4 4-0.8,28.3±0.5,36.3±1.1.and in the control group they respectively were 8.5±1.0,12.3±1.1,17.4±1.2,20.4±stronger than those in normal pregnant women at different gestational weeks(P<0.05).However,the expression tendency of bcl-2 mRNA and proten was converse to the expression tendency of Bax.Conclusion The expressions of LOX-1,caspase-3,and Bax are upregulated in placentas of preeclampsia patients,while bcl-2 iS downregulated,both of which are associated with the pathogenesis of preeclampsia.

Expression and significance of anti-apoptotic gene Bag-1 and Bcl-2 in colorectal cancer / 中国现代普通外科进展

Objective:To investigate the expressions of Bag-1 and Bcl-2 in colorectal cancer and evaluate their clinical significance.Methods:Bag-1 and Bcl-2 expressions were studied by immunohistochemical Streptavidin-Biotin-Peroxidase Complex(SABC)method in 64 samples of colorectal cancer tissues,10 normal colorectal tissues.Results:Bag-1 was positively related to the tumor grade,distant metastasis,stages of Dukes and prognosis,but was not related to the pathological cell types,tumor diameter,depth of invasion and lymph node metastasis.Bcl-2 was not correlated to these clinicopathologic factors.There was a positive correlation between Bag-1 and Bcl-2(r=0.475).Conclusion:The over expression of Bag-1 and Bcl-2 protein in colorectal cancer can affect the generation of colorectal cancer by participating in the regulation of apoptosis.

THC SIGNIFICANCC OF BCL-2 EXPRESSION IN GASTRIC ADENOCARCINOMA AND PRECANCEROUS LESIONS / 肿瘤研究与临床

Objective To study the influence of bcl-2 on gastric tumorigenesis and its significance.Methods The expression was observed in 20 normal gastric mucosa, 38 gastric epithelial dysplasia(GED)and 52 gastric adenocarcinomas (GAC) by immunohistochemical method. Results in bcl-2 expression,significant difference was found between GED and normal gastric mucosa (P