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An N-terminal region of translationally controlled tumor protein is required for its antiapoptotic activity

Abstract

Bcl-xL plays a critical role in maintaining cell survival. However, the relationship between the potential interaction of Bcl-xL with other cytosolic proteins and the regulation of cell survival remains incompletely defined. We have identified translationally controlled tumor protein (TCTP), a multifunctional protein, as a novel antiapoptotic Bcl-xL-interacting protein. TCTP interacted in vivo and in vitro with Bcl-xL, and their sites have been mapped to an N-terminal region of TCTP and the Bcl-2 homology domain 3 of Bcl-xL. Consistent with a role in maintaining T-cell survival during activation, TCTP was significantly upregulated in murine T cells activated by T-cell antigen receptor (TCR) ligation and CD28 costimulation, which was correlated with the upregulation of Bcl-xL in activated T cells. Moreover, downregulation of TCTP expression by antisense technology in T cells results in the increase of T-cell apoptosis. Furthermore, the N-terminal region of TCTP was required for its ability to inhibit apoptosis. In conclusion, this study has demonstrated that an N-terminal region of a cytosolic protein, TCTP, is required for its binding to Bcl-xL and for its antiapoptotic activity.

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Abbreviations

TCTP:

translationally controlled tumor protein

BH3 domain:

Bcl-2 homology domain 3

TNT:

in vitro transcription and translation

GST:

glutathione S-transferase

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Acknowledgements

We are grateful to Drs DP Huston, L-Y Yu-Lee, TH Tan, S Zhang, B Ng, H Lu, and JP Aumais at Baylor, H Cantor and J Ritz at Harvard, Dr SM MacDonald at the Johns Hopkins, and Drs E Guillaume and JC Sanchez at Hopital Cantonal Universitaire de Geneve for suggestion or reagents, Drs MA Mancini and F Kheradmand at Baylor for the use of confocal and fluorescence microscopes, and Ms K Franks and her associates in our section for assistance. This work was partially supported by funds from NIH Grants AI054514, P30 DK56238, and P20 CA103698, development support at Baylor, the Kostas Foundation, the Law Foundation, the Myositis Association of America, the American Heart Association-Texas Affiliate, and the Leukemia & Lymphoma Society and Myeloproliferative Disorders Foundation. X-F Yang is a Chao Family Scholar of Medicine.

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Correspondence to Xiao-Feng Yang.

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Yang, Y., Yang, F., Xiong, Z. et al. An N-terminal region of translationally controlled tumor protein is required for its antiapoptotic activity. Oncogene 24, 4778–4788 (2005). https://doi.org/10.1038/sj.onc.1208666

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Keywords

  • Bcl-xL
  • TCTP
  • apoptosis
  • protein interaction

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