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J. Biol. Chem., Vol. 277, Issue 30, 27200-27209, July 26, 2002
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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-Asp7
Polypyrimidine Tract-binding Proteins Are Cleaved by
Caspase-3 during Apoptosis*
§
Ile,
Leu-Tyr-Thr-Asp139
Ser, and
Ala-Ala-Val-Asp172
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.
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.
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