查锡良
长期从事医学生物化学与分子生物学、糖生物学、肿瘤分子生物学等领域的科研工作
个性化签名
- 姓名:查锡良
- 目前身份:
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学术头衔:
博士生导师
- 职称:-
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学科领域:
生物化学
- 研究兴趣:长期从事医学生物化学与分子生物学、糖生物学、肿瘤分子生物学等领域的科研工作
查锡良,男,1949年2月生。毕业于上海医科大学。现任复旦大学基础医学院副院长,生化教研室主任,卫生部糖复合物重点实验室主任,教授,博导。1983年获生物化学专业硕士学位,1987年获生物化学专业博士学位。1984-1986年于美国密执安大学(Ann Arbor)作博士后,从事细胞分化时表面糖链结构研究。1991-1993年于加拿大马尼托巴大学生物化学与与分子生物学系作访问学者,进行细胞信号转导研究。自1977年起进入原上海医科大学生化教研室任教,1986年起依次任讲师,副教授,教授。
长期从事医学生物化学与分子生物学、糖生物学、肿瘤分子生物学等领域的教学和科研工作,1998年以来共发表国内外学术论文90余篇。近五年本人研究重点为,从分子、细胞和动物水平研究重要生长因子受体、E-钙粘蛋白的糖链对其与配体的结合、蛋白质合成转运和降解、细胞的信号转导、细胞凋亡等方面都有相应的作用。在糖蛋白的单个糖基化位点、单个糖基的作用研究取得了新的成果。在研究抑癌基因PTEN在人肝癌细胞中的表达及其调控方面,发现该基因存在mRNA水平的调控,并对该基因的转录因子作了详尽的研究,为深入寻找肿瘤治疗的靶分子提供了线索。承担和参与了一系列国家自然科学基金面上项目、重点项目、973项目、863项目、上海市教委重点项目和美国CMB项目;作为上海市优秀学科带头人承担多项上海市科委项目。作为第一完成人共获上海市科技进步奖二等奖等奖项5项。曾获卫生部中青年医学科技之星,卫生部有突出贡献的中青年专家,宝钢优秀教师奖,全国优秀教师等殊荣,1995年获国务院特殊津贴。
兼任中国生化与分子生物学学会副理事长;中科院生化细胞所国家分子生物学重点实验室学术委员会副主任;中科院上海生命科学院学术委员会委员;《生物化学与生物物理学报》学务编委。
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主页访问
1957
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关注数
0
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成果阅读
268
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成果数
7
查锡良, Zhen Xu‡§†, Tomohiko Fukuda‡§, You Li‡, Xiliang Zha¶, Jun Qin , and Chuanyue Wu‡**
Vol. 280, No. 30, Issue of July 29, pp. 27631-27637, 2005,-0001,():
-1年11月30日
How cells couple and uncouple regulation of cellular processes such as shape change and survival is an important question in molecular cell biology. PINCH-1, a widely expressed protein consisting of five LIM domains and a C-terminal tail, is an essential focal adhesion protein with multiple functions including regulation of the integrin-linked kinase (ILK) level, cell shape, and survival signaling. We show here that the LIM1-mediated interaction with ILK regulates all these three processes. By contrast, the LIM4-mediated interaction with Nck-2, which regulates cell morphology and migration, is not required for the control of the ILK level and survival. Remarkably, a short 15-residue tail C-terminal to LIM5 is required for both cell shape modulation and survival, albeit it is not required for the control of the ILK level. The C-terminal tail not only regulates PINCH-1 localization to focal adhesions but also functions after it localizes there. These findings suggest that PINCH-1 functions as a molecular platform for coupling and uncoupling diverse cellular processes via overlapping but yet distinct domain interactions.
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查锡良, Xiu-Mei Cai, Bei-Bei Tao, Li-Ying Wang, , Yu-Long Liang, Jia-Wei Jin, Yong Yang, Ya-Li Hu and Xi-Liang Zha, *
Int. J. Cancer: 117, 905-912 (2005),-0001,():
-1年11月30日
PTEN is a major tumor suppressor gene that has been shown to inhibit cell invasion. Its mutation has been found in 20-40% of malignant gliomas. Meanwhile, the type III EGFR mutation (EGFRvIII), which was frequently found in gliomas, promoted cell invasion. In the present study, the effects of PTEN on cell invasion were investigated in U87DEGFR glioblastoma cells with EGFRvIII expression but missing PTEN. The cell invasion was downregulated by transfection of phosphatase-active forms of PTEN (wild-type and G129E) but not by PTEN (C124A) with an inactive phosphatase domain; the effects were correlated with decreased tyrosine phosphatase levels of FAK at Tyr397, which was increased by EGFRvIII. Overexpression of FAK mutant (Y397F) could partially mimic the effect of PTEN on cell invasion. Although EGFRvIII increased the levels of P-Akt and PTEN eliminated it, PI-3K inhibitors, wortmannin or Ly294002, could not decrease the cell invasion. In conclusion, PTEN could inhibit cell invasion even in the presence of the constitutively active EGFR; this inhibition depended on its protein phosphatase activity, partially by dephosphorylating FAK, but not depended on its lipid phosphatase activity.
EGFRvIII, PTEN, FAK, invasion
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查锡良, Yu-Long Lianga, Yi Fua, Si-Gang Chena, Xiu-Mei Caia, Jian-Min Sua, Jia-Wei Jina, Dong-Zhu Maa, Zeng-Xia Lia, Wen Zhanga, Xiliang Zhaa, b, *
FEBS Letters 558(2004)107-113,-0001,():
-1年11月30日
Evidence has been emerging to suggest that integrin could induce growth inhibition in some cell types. Some of the molecular mechanisms underlying growth arrest have been elucidated. We reported here that overexpression of integrin L1 imposed a growth inhibitory e
Integrin, p21CIP1, Hepatocellular carcinoma cell line, Trans, c, r, i, p, t, ional regulation, Promoter activity
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查锡良, Lineng Zhang, , Qiang Yu, Jianyu He and Xiliang Zha
Molecular and Cellular Biochemistry 262: 25-33, 2004.,-0001,():
-1年11月30日
N expression at both mRNA and protein levels compared with immortalized L02 hepatic cells. PTEN mRNA in SMMC-7721 hepatoma cells could be reduced by TGF-βI treatment. We also found that the phosphorylation levels of FAK in both of the hepatoma cell lines were higher than that in L02 hepatic cells. Transient expression of the PTEN gene in SMMC-7721 and HepG2 hepatoma cells resulted in decreased FAK phosphorylation. The level of FAK tyrosine phosphorylation appeared to be inversely correlated with the level of the PTEN protein. In summary, our results indicated that the function of the PTEN gene in hepatocarcinomas may be impaired mainly through point mutations and expression deficiency and that the defect of PTEN in tumor cells could alter the phosphorylation of FAK. (Mol Cell Biochem 262: 25–33, 2004)
PTEN,, mutation,, expression,, FAK,, hepatocellular carcinoma
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查锡良, Yi Fang, Liying Wang, Jiawei Jin and Xiliang Zha
Eur. J. Biochem. 268, 4513-4519 (2001),-0001,():
-1年11月30日
Most cell lines are resistant to tumor necrosis factor-a (TNF-a) cytotoxicity and require cotreatment of TNF-a with cycloheximide (Chx) to undergo apoptosis. Recently, the serine/threonine protein kinase, protein kinase B has been demonstrated to protect cells from apoptosis induced by TNF-a. In this study, we have shown that the human hepatocellular carcinoma cell line, SMMC-7721, was insensitive to TNF-a cytotoxicity and underwent apoptosis quickly in the presence of TNF-a and Chx. PKB levels decreased during TNF-a/Chx-induced apoptosis. No significant change in PKB levels was found in the presence of TNF-a or Chx alone. It seemed that the level of PKB closely correlated with apoptosis. The protein level of focal adhesion kinase (FAK) was reduced by 66% by transfecting FAK antisense cDNA recombinant vector into SMMC-7721 cells. We determined the apoptosis-induced effect of TNF-a/Chx on the FAK antisense cDNA transfectant cells. The results indicated that the percentage of apoptotic cells was enhanced at lower doses of TNF-a (10, 20 or 50U: mL21) and decreased at a higher dose of TNF-a (1000 U: mL21) in the transfected cells as compared to the control. Correspondingly, in the FAK antisense cDNA transfectant cells treated with lower doses of TNF-a in presence of 10 mg: mL21 Chx, the PKB level was lower, but in the FAK antisense cDNA transfectants treated with higher doses of TNF-a in presence of 10 mg:mL21 Chx, the PKB level was higher. In response to TNF-a alone, FAK antisense cDNA transfectants showed a decrease in the level of PKB. However, in the case of TNF-a cotreated with wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PtdIns3K), the FAK antisense cDNA transfectants produced significantly less amounts of PKB than the control. It seemed that FAK could stimulate PKB levels through a pathway not involving PtdIns3K. These results suggest that FAK can affect the sensitivity of SMMC-7721 cells to TNF-a/Chx-induced apoptosis in a biphasic manner by regulating PKB levels.
focal adhesion kinase, protein kinase B, SMMC-7721 cells, tumor necrosis factor-a, cycloheximide, apoptosis.,
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查锡良, Ting Cai, Qun-Ying Lei, Li-Ying Wang, and Xi-Liang Zha
Biochemical and Biophysical Research Communications 274, 519-525 (2000),-0001,():
-1年11月30日
Integrins are a family of cell surface adhesion molecules which mediate cell adhesion and initiate signaling pathways that regulate cell spreading, migration, differentiation, and proliferation. TGF-b is a multifunctional factor that induces a wide variety of cellular processes. In this study, we show that, TGF-b1 treatment enhanced the amount of a5b1 integrin on cell surface, the mRNA level of a5 subunit, and subsequently stimulated cell adhesion onto a fibronectin (Fn) and laminin (Ln) matrix in SMMC-7721 cells. TGF-b1 could also promote cell migration. Furthermore, our results showed that TGF-b1 treatment stimulated the tyrosine phosphorylation level of FAK, which can be activated by the ligation and clustering of integrins. PTEN can directly dephosphorylate FAK, and the results that TGF-b1 could down-regulate PTEN at protein level suggested that TGF-b1 might stimulate FAK phosphorylation through increasing integrin signaling and reducing dephosphorylation of FAK. These studies indicated that TGF-b1 and integrin-mediated signaling act synergistically to enhance cell adhesion and migration and affect downstream signaling molecules of hepatocarcinoma cells.
integrin, -b1, focal adhesion kinase, PTEN, cell adhesion, cell migration.,
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查锡良, Guo-Fei Zhou, Feng Ye, Li-Huan Cao and Xi-Liang Zha
Molecular and Cellular Biochemistry 207: 49-55, 2000.,-0001,():
-1年11月30日
Integrin a 5β1 and a 2β1 are the major integrin receptors in human hepatocytes. However, in human hepatocellular carcinoma cells it was found that the expression of integrin a 5β1 was decreased and another integrin a 6 β1 increased. In this study, the SMMC7721 human hepatocellular carcinoma cells cotransfected or singlely transfected with integrin a 5 and/or β 1 cDNAs were established, and designated a 5β 1.6-7721, a 5.3-7721, and β 1.6-7721 cell lines, respectively. Transfection with cDNAs of integrin a 5 and β 1 subunits resulted in the over expression of each integrin and modified biological properties, including a slowed growth rate, changes in the cell cycle from 15.5% of control cells in the G2/M phase to 12.1%, 9.6% and 9.4% in a 5.3-7721, β 1.6-7721, a 5 β 1.6-7721, respectively, and a decrease in the Cell Mitosis Index from 1.6 in controls to 0.96, 0.95, and 0.72, and 34%, 28% and 52% derived from colony forming ability, respectively. Tumorigenicity was also tested in nude mice with inoculation of cells subcutaneously. Tumor masses growing in nude mice following inoculation with b 1.6-7721, and a 5 β 1.6-7721 cells weighed only 52% or 31% those of control cells. These results indicated that deletion or low expression of integrin a 5 β 1 may play an important role in the development of hepatocellular carcinoma. Therefore, induction of expression of the integrin a 5 β 1 in malignant cells could be a potential means of treating hepatocellular carcinoma. (Mol Cel Biochem 207: 49-55, 2000)
integrin,, human hepatocelluar carcinoma,, tumorigenicity
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