Oncogenic Ras blocks cell cycle progression and inhibits p34cdc2 kinase in activated Xenopus egg extracts.
The effect of purified, bacterially expressed human RasH proteins on embryonic cell cycle progression in activated Xenopus egg extracts was studied. Bacterially expressed human oncogenic RasH protein is able to block the progression of the Xenopus embryonic cell cycle into M-phase. In contrast, the corresponding normal human Ras protein is relatively ineffective when assayed in a like manner. The observed arresting activity can be blocked by the addition of Y13-259 anti-Ras monoclonal antibody but not by nonspecific IgG. Oncogenic Ras also induces unique morphological changes in the reconstituted nuclei; the nuclei appear to be enlarged, and the chromatin partially condenses into fiber-like structures. This induced arrest is associated with suppression of p34cdc2 kinase activity, indicating that the oncogenic Ras protein induces the arrest by inactivating p34cdc2. This inactivation by oncogenic Ras protein does not result from inhibition of the synthesis of cyclin B or of the binding of the newly synthesized cyclin B to the p34cdc2.
Pan
B T
BT
Department of Surgery, University of Kentucky Medical Center, Lexington 40536.
Chen
C T
CT
Lin
S M
SM
D000818:Animals; D001419:Bacteria / Q000235:genetics; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D016213:Cyclins / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D006801:Humans; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism*; D010063:Ovum / Q000166:cytology / Q000201:enzymology; D014981:Xenopus
D016213:Cyclins; D016203:CDC2 Protein Kinase; D015689:Oncogene Protein p21(ras)