An effector peptide from glutathione-S-transferase-pi strongly and selectively blocks mitotic signaling by oncogenic ras-p21.
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.
Chie
Lyndon
L
Department of Pathology and Laboratory Medicine, New York Harbor VA Medical Center, Brooklyn, NY 11209, USA.
Adler
Victor
V
Friedman
Fred K
FK
Chung
Denise
D
Pincus
Matthew R
MR
D000818:Animals; D005260:Female; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000037:antagonists & inhibitors*; D009865:Oocytes / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014981:Xenopus
D007527:Isoenzymes; D010455:Peptides; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D048031:JNK Mitogen-Activated Protein Kinases; D015689:Oncogene Protein p21(ras)