PROMOTION OF CELL SURVIVAL BY ADENOVIRUS E1B 19K PROTEIN
PROMOTION OF CELL SURVIVAL BY ADENOVIRUS E1B 19K PROTEIN
批准号:
2517548
负责人:
GOVINDASWAMY CHINNADURAI
金额:
$21.15万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1995
资助国家:
美国
项目状态:
已结题
起止时间:
1995-09-30 至 1999-06-30
关键词:
Adenoviridae apoptosis biological signal transduction calcium binding protein calcium flux cell free system cell transformation gene expression guanine nucleotide binding protein host organism interaction immunofluorescence technique immunoprecipitation laboratory mouse laboratory rat molecular cloning mutant necrosis oncoproteins phosphodiesterases protein purification protein structure function tissue /cell culture transfection virus DNA virus protein
中文摘要
受调控的细胞死亡是消除特异性的重要过程
英文摘要
Regulated cell death is an important process for elimination of specific
cells in multicellular organisms during normal development and
homeostasis. Deregulated cell death can lead to degenerative diseases
such as Alzheimer's and Parkinson's disease and AIDS. Inhibition of cell
death can also lead to oncogenesis and resistance to chemotherapeutic
treatments. The E1B 19 kD protein of human adenovirus (Ad) is an
important member of a class of proteins involved in suppression of cell
death. It promotes the survival of cells infected with adenovirus or
exposed to several external cell death (apoptosis)-inducing stimuli. The
19 kD protein is functionally similar to the Bc1-2 protooncoprotein and
the Epstein-Barr virus BHRF1 protein. The 19 kD and Bcl-2 proteins appear
to share common sequence motifs essential for inhibition of cell death.
We have identified and cloned four cellular proteins that interact with
the 19 kD (19-kD-interacting proteins, Nip1 to 4) and the Bc1-2 proteins
through these homologous sequence motifs. To elucidate the common
mechanism of cell death inhibition by the 19 kD and Bc1-2 proteins, we
propose to functionally characterize the various Nips. The role of these
cellular proteins in regulating cell death induced by different
mechanisms will be examined using multiple cell death/survival assays.
Endogenous expression and subcellular localization of these proteins in
response to exposure to various cell death stimuli will be examined.
Some of these cellular proteins contain intriguing sequence homologies.
Nip1 shares limited homology with the catalytic domain of certain
mammalian phosphodiesterases. Nip2 shares homology with the (GTPase-
stimulating protein RhoGAP. Nip3 is localized in the mitochondria. Nip2
and Nip4 contain putative Ca2+ -binding motifs. These proteins will be
characterized to elucidate their role in signal transduction and calcium
mobilization. Since the cell death effectors induced by adenovirus
infection is not known, we propose to use a cell free in vitro cell death
system to identify and clone such effector(s). Since inactivation of
survival-promoting activities of the 19 kD and Bc1-2 proteins would be
advantageous, we propose to explore the possibility of using mutants
defective in the survival domains as dominant negative inhibitors.
Similarly, peptides corresponding to the survival domains will also be
examined as competitive inhibitors of the 19 kD and Bc1-2 proteins. Thus,
our proposal may illuminate the mechanism by which the 19 kD and Bc1-2
proteins suppress cell death and also reveal strategies to interfere with
their activities.
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批准号:6957117
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E1A-CtBP interactions in oncogenic transformations
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批准号:7898951
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资助金额:$27.93万
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E1A-CtBP interactions in oncogenic transformations
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资助金额:$27.93万
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负责人:GOVINDASWAMY CHINNADURAI
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依托单位:
Modulation of Oncogenesis by E1A--Role of CtBP and CtIP
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批准号:6871359
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项目类别:
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资助金额:$22.62万
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财政年份:2001
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负责人:GOVINDASWAMY CHINNADURAI
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依托单位:
E1A-CtBP interactions in oncogenic transformations
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批准号:7499104
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项目类别:
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资助金额:$27.93万
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财政年份:2001
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负责人:GOVINDASWAMY CHINNADURAI
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依托单位:
E1A-CtBP interactions in oncogenic transformations
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批准号:8104098
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项目类别:
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资助金额:$27.09万
-
财政年份:2001
-
负责人:GOVINDASWAMY CHINNADURAI
-
依托单位:
Modulation of Oncogenesis by E1A--Role of CtBP and CtIP
-
批准号:6633611
-
项目类别:
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资助金额:$22.62万
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财政年份:2001
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负责人:GOVINDASWAMY CHINNADURAI
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依托单位:
APOPTOSIS REGULATION BY VIRAL AND CELLULAR PROTEINS
-
批准号:6172640
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项目类别:
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资助金额:$27.58万
-
财政年份:1999
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负责人:GOVINDASWAMY CHINNADURAI
-
依托单位:
APOPTOSIS REGULATION BY VIRAL AND CELLULAR PROTEINS
-
批准号:2907616
-
项目类别:
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资助金额:$23.52万
-
财政年份:1999
-
负责人:GOVINDASWAMY CHINNADURAI
-
依托单位:
Apoptosis Regulation by Adenovirus and Cellular Genes
-
批准号:8130173
-
项目类别:
-
资助金额:$28.8万
-
财政年份:1999
-
负责人:GOVINDASWAMY CHINNADURAI
-
依托单位:
Apoptosis Regulation by Adenovirus and Cellular Genes
-
批准号:8657981
-
项目类别:
-
资助金额:$27.94万
-
财政年份:1999
-
负责人:GOVINDASWAMY CHINNADURAI
-
依托单位:
E1A-CtBP interactions in oncogenic transformations
-
批准号:7383289
-
项目类别:
-
资助金额:$27.93万
-
财政年份:1999
-
负责人:GOVINDASWAMY CHINNADURAI
-
依托单位:
APOPTOSIS REGULATION BY VIRAL AND CELLULAR PROTEINS
-
批准号:6375655
-
项目类别:
-
资助金额:$28.2万
-
财政年份:1999
-
负责人:GOVINDASWAMY CHINNADURAI
-
依托单位:
Apoptosis Regulation by Adenovirus and Cellular Genes
-
批准号:7253239
-
项目类别:
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资助金额:$28.23万
-
财政年份:1999
-
负责人:GOVINDASWAMY CHINNADURAI
-
依托单位:
Apoptosis Regulation by Adenovirus and Cellular Genes
-
批准号:7449764
-
项目类别:
-
资助金额:$28.23万
-
财政年份:1999
-
负责人:GOVINDASWAMY CHINNADURAI
-
依托单位:
Apoptosis Regulation by Adenovirus and Cellular Genes
-
批准号:6953596
-
项目类别:
-
资助金额:$29.77万
-
财政年份:1999
-
负责人:GOVINDASWAMY CHINNADURAI
-
依托单位:
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