Previous Article | Next Article 
Molecular and Cellular Biology, May 2003, p. 3623-3635, Vol. 23, No. 10
0270-7306/03/$08.00+0 DOI: 10.1128/MCB.23.10.3623-3635.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
FAP-1 Association with Fas (Apo-1) Inhibits Fas Expression on the Cell Surface
Vladimir N. Ivanov,1 Pablo Lopez Bergami,1 Gabriel Maulit,1 Taka-Aki Sato,2 David Sassoon,3 and Ze'ev Ronai1*
Ruttenberg Cancer Center,1
Department of Molecular and Developmental Biology, Mount Sinai School of Medicine, New York, New York 10029,3
Department of Pathology, Columbia University, New York, New York 100322
Received 22 October 2002/
Returned for modification 11 December 2002/
Accepted 18 February 2003
As revealed by intracellular pools of nonactive Fas (Apo-1), export of Fas to the cell surface is often impaired in human tumors, thereby inactivating Fas ligand-mediated apoptosis. Here, we demonstrate that association with Fas-associated phosphatase 1 (FAP-1) attenuates Fas export to the cell surface. Forced expression of FAP-1 reduces cell surface Fas levels and increases the intracellular pool of Fas within the cytoskeleton network. Conversely, expression of dominant-negative forms of FAP-1, or inhibition of FAP-1 expression by short interfering RNA, efficiently up-regulates surface expression of Fas. Inhibition of Fas surface expression by FAP-1 depends on its association with the C terminus of Fas. Mutation within amino acid 275 results in decreased association with FAP-1 and greater export of Fas to the cell surface in melanomas, normal fibroblasts, or Fas null cells. Identifying the role of FAP-1 in binding to, and consequently inhibition of, Fas export to the cell surface provides novel insight into the mechanism underlying the regulation of Fas trafficking, which is commonly impaired in advanced tumors with FAP-1 overexpression.
* Corresponding author. Mailing address: Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, One Gustave L. Levy Pl., Box 1130, New York, NY 10029-6574. Phone: (212) 659-5571. Fax: (212) 849-2425. E-mail:
zeev.ronai{at}mssm.edu.
Molecular and Cellular Biology, May 2003, p. 3623-3635, Vol. 23, No. 10
0022-538X/03/$08.00+0 DOI: 10.1128/MCB.23.10.3623-3635.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Park, J.-W., Kim, H. P., Lee, S.-J., Wang, X., Wang, Y., Ifedigbo, E., Watkins, S. C., Ohba, M., Ryter, S. W., Vyas, Y. M., Choi, A. M. K.
(2008). Protein Kinase C{alpha} and {zeta} Differentially Regulate Death-Inducing Signaling Complex Formation in Cigarette Smoke Extract-Induced Apoptosis. J. Immunol.
180: 4668-4678
[Abstract]
[Full Text]
-
Huang, W., Zhu, C., Wang, H., Horvath, E., Eklund, E. A.
(2008). The Interferon Consensus Sequence-binding Protein (ICSBP/IRF8) Represses PTPN13 Gene Transcription in Differentiating Myeloid Cells. J. Biol. Chem.
283: 7921-7935
[Abstract]
[Full Text]
-
Jin, B., Tao, Q., Peng, J., Soo, H. M., Wu, W., Ying, J., Fields, C. R., Delmas, A. L., Liu, X., Qiu, J., Robertson, K. D.
(2008). DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis and immune function. Hum Mol Genet
17: 690-709
[Abstract]
[Full Text]
-
Ivanov, V. N., Zhou, H., Hei, T. K.
(2007). Sequential Treatment by Ionizing Radiation and Sodium Arsenite Dramatically Accelerates TRAIL-Mediated Apoptosis of Human Melanoma Cells. Cancer Res.
67: 5397-5407
[Abstract]
[Full Text]
-
Zhang, W., Tong, Q., Conrad, K., Wozney, J., Cheung, J. Y., Miller, B. A.
(2007). Regulation of TRP channel TRPM2 by the tyrosine phosphatase PTPL1. Am. J. Physiol. Cell Physiol.
292: C1746-C1758
[Abstract]
[Full Text]
-
Halle, M., Liu, Y.-C., Hardy, S., Theberge, J.-F., Blanchetot, C., Bourdeau, A., Meng, T.-C., Tremblay, M. L.
(2007). Caspase-3 Regulates Catalytic Activity and Scaffolding Functions of the Protein Tyrosine Phosphatase PEST, a Novel Modulator of the Apoptotic Response. Mol. Cell. Biol.
27: 1172-1190
[Abstract]
[Full Text]
-
Rosner, D., Stoneman, V., Littlewood, T., McCarthy, N., Figg, N., Wang, Y., Tellides, G., Bennett, M.
(2006). Interferon-{gamma} Induces Fas Trafficking and Sensitization to Apoptosis in Vascular Smooth Muscle Cells via a PI3K- and Akt-Dependent Mechanism. Am. J. Pathol.
168: 2054-2063
[Abstract]
[Full Text]
-
Yeh, S.-H., Wu, D.-C., Tsai, C.-Y., Kuo, T.-J., Yu, W.-C., Chang, Y.-S., Chen, C.-L., Chang, C.-F., Chen, D.-S., Chen, P.-J.
(2006). Genetic Characterization of Fas-Associated Phosphatase-1 as a Putative Tumor Suppressor Gene on Chromosome 4q21.3 in Hepatocellular Carcinoma. Clin. Cancer Res.
12: 1097-1108
[Abstract]
[Full Text]
-
Ivanov, V. N., Ronai, Z., Hei, T. K.
(2006). Opposite Roles of FAP-1 and Dynamin in the Regulation of Fas (CD95) Translocation to the Cell Surface and Susceptibility to Fas Ligand-mediated Apoptosis. J. Biol. Chem.
281: 1840-1852
[Abstract]
[Full Text]
-
Wang, X., Wang, Y., Zhang, J., Kim, H. P., Ryter, S. W., Choi, A. M. K.
(2005). FLIP Protects against Hypoxia/Reoxygenation-Induced Endothelial Cell Apoptosis by Inhibiting Bax Activation. Mol. Cell. Biol.
25: 4742-4751
[Abstract]
[Full Text]
-
Ivanov, V. N., Hei, T. K.
(2004). Arsenite Sensitizes Human Melanomas to Apoptosis via Tumor Necrosis Factor {alpha}-mediated Pathway. J. Biol. Chem.
279: 22747-22758
[Abstract]
[Full Text]
-
Bhoumik, A., Jones, N., Ronai, Z.
(2004). Transcriptional switch by activating transcription factor 2-derived peptide sensitizes melanoma cells to apoptosis and inhibits their tumorigenicity. Proc. Natl. Acad. Sci. USA
101: 4222-4227
[Abstract]
[Full Text]