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Originally published In Press as doi:10.1074/jbc.M203887200 on May 9, 2002

J. Biol. Chem., Vol. 277, Issue 30, 27200-27209, July 26, 2002
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Polypyrimidine Tract-binding Proteins Are Cleaved by Caspase-3 during Apoptosis*

Sung Hoon Back§, Sejeong Shin, and Sung Key JangDagger §

From the § National Research Laboratory and the  National Creative Research Center for Biomolecular Interaction, Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, San31, Hyoja-Dong, Pohang, Kyungbuk 790-784, Korea

The polypyrimidine tract-binding protein (PTB), an RNA-binding protein, is required for efficient translation of some mRNAs containing internal ribosomal entry sites (IRESs). Here we provide evidence that the addition of apoptosis-inducing agents to cells results in the cleavage of PTB isoforms 1, 2, and 4 by caspase-3. This cleavage of PTB separated the N-terminal region, containing NLS-RRM1, from the C-terminal region, containing RRM2-3-4. Our data indicate that there are three noncanonical caspase-3 target sites in PTBs, namely Ile-Val-Pro-Asp7down-arrow Ile, Leu-Tyr-Thr-Asp139down-arrow Ser, and Ala-Ala-Val-Asp172down-arrow Ala. The C-terminal PTB fragments localized to the cytoplasm, as opposed to the nucleus where most intact PTBs are found. Moreover, these C-terminal PTB fragments inhibited translation of polioviral mRNA, which contains an IRES element requiring PTB for its activation. This suggests that translation of some IRES-containing mRNAs is regulated by proteolytic cleavage of PTB during apoptosis.


* This work was supported in part by the G7, National Research Laboratory, and Molecular Medicine Research Group Programs of the Ministry of Science and Technology and by a grant from the Korea Science and Engineering Foundation through the Protein Network Research Center.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, San31, Hyoja-Dong, Pohang, Kyungbuk 790-784, Korea. Tel.: 82-54-279-2298; Fax: 82-54-279-8009; E-mail: sungkey@postech.ac.kr.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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