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An Effector Peptide from Glutathione-S-Transferase-pi Strongly and Selectively Blocks Mitotic Signaling by Oncogenic ras-p21

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Abstract

Oncogenic ras-p21 directly activates jun-N-terminal kinase (JNK) and its substrate, jun as a unique step on its mitogenic signal transduction pathway. This activation is blocked by the specific JNK-jun inhibitor, glutathione-S-transferase-pi (GST-pi). Four domains of GST-pi have been implicated in this regulatory function: 34–50, 99–121, 165–182, and 194–201. The 34–50 domain is unique in that it does not affect GST-pi binding to JNK-jun but blocks jun phosphorylation by JNK. We now find that it completely blocks oncogenic (Val 12-) ras-p21–induced oocyte maturation but has no effect on insulin-induced oocyte maturation. Because the latter process requires activation of wild-type ras-p21, this peptide appears to be specific for inhibiting only the oncogenic form of ras-p21, suggesting its use in treating ras-induced tumors.

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Chie, L., Adler, V., Friedman, F.K. et al. An Effector Peptide from Glutathione-S-Transferase-pi Strongly and Selectively Blocks Mitotic Signaling by Oncogenic ras-p21. J Protein Chem 23, 235–238 (2004). https://doi.org/10.1023/B:JOPC.0000026419.54902.bb

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