Calmodulin binding to the Fas-Mediated death-inducing signaling complex in cholangiocarcinoma cells.

Calmodulin binding to the Fas-Mediated death-inducing signaling complex in cholangiocarcinoma cells. Research Abstract Details 

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Calmodulin binding to the Fas-Mediated death-inducing signaling complex in cholangiocarcinoma cells. Abstract Text:

Yabing Chen,Pritish Pawar,George Pan,Liping Ma,Hui Liu,Jay M McDonald,Yabing Chen,Pritish Pawar,George Pan,Liping Ma,Hui Liu,Jay M McDonald,

We have previously demonstrated that the antagonists of calmodulin (CaM) induce apoptosis of cholangiocarcinoma cells partially through Fas-mediated apoptosis pathways. Recently, CaM has been shown to bind to Fas, which is regulated during Fas or CaM antagonist-mediated apoptosis in Jurkat cells and osteoclasts. Accordingly, the present studies were designed to determine whether Fas interacts with CaM in cholangiocarcinoma cells and to elucidate its role in regulating Fas-mediated apoptosis. CaM bound to Fas in cholangiocarcinoma cells. CaM was identified in the Fas-mediated death inducing signaling complex (DISC). The amount of CaM recruited into the DISC was increased after Fas-stimulation, a finding confirmed by immunofluorescent analysis that demonstrated increased membrane co-localization of CaM and Fas upon Fas-stimulation. Consistently, increased Fas microaggregates in response to Fas-stimulation were found to bind to CaM. Fas-induced recruitment of CaM into the DISC was inhibited by the Ca(2+) chelator, EGTA, and the CaM antagonist, trifluoperazine (TFP). TFP decreased DISC-induced cleavage of caspase-8. Further, inhibition of actin polymerization, which has been demonstrated to abolish DISC formation, inhibited the recruitment of CaM into the DISC. These results suggest an important role of CaM in mediating DISC formation, thus regulating Fas-mediated apoptosis in cholangiocarcinoma cells. Characterization of the role of CaM in Fas-mediated DISC formation and apoptosis signaling may provide important insights in the development of novel therapeutic targets for cholangiocarcinoma. J. Cell. Biochem. 103: 788-799, 2008. (c) 2007 Wiley-Liss, Inc.

Calmodulin binding to the Fas-Mediated death-inducing signaling complex in cholangiocarcinoma cells. Publishing Authors By Initials

Y Chen,P Pawar,G Pan,L Ma,H Liu,JM McDonald,Y Chen,P Pawar,G Pan,L Ma,H Liu,JM McDonald,

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Calmodulin binding to the Fas-Mediated death-inducing signaling complex in cholangiocarcinoma cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of cellular biochemistry

VOLUME: 103

Page Numbers: 788-99

Journal Abbreviation: J. Cell. Biochem.

ISSN: 0730-2312

DAY: 15

MONTH: Feb

YEAR: 2008

Calmodulin binding to the Fas-Mediated death-inducing signaling complex in cholangiocarcinoma cells. Information

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LANGUAGE: eng

NlmUniqueID: 8205768

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Grant and Affiliation Information for Calmodulin binding to the Fas-Mediated death-inducing signaling complex in cholangiocarcinoma cells.

AFFILIATION: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.

Country: United States

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MEDLINETA: J Cell Biochem

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