The proto-oncogene Crk-II enhances apoptosis by a Ras-dependent, Raf-1/MAP kinase-independent pathway

Biochemical and Biophysical Research Communications
M ParrizasD Le Roith

Abstract

Human embryonic kidney 293 cells and 293 cells overexpressing different amounts of the adaptor protein Crk-II (ranging from 3- to 10-fold higher levels than the parental cell line) were examined for their ability to undergo apoptosis when maintained in control and serum-free (SF) medium. Parental 293 cells undergo apoptosis only when deprived of serum for prolonged periods of time (24-48 h). On the other hand, 293 cells overexpressing different levels of Crk-II present detectable levels of apoptosis as measured by DNA fragmentation when grown in control medium, with a marked increase when they are deprived of serum for 12-48 h. To determine the pathways involved in Crk-II-induced apoptosis, Crk-II overexpressing cells were transiently transfected with a dominant-negative Ras construct (N17-Ras). Compared to cells transfected with control vectors, the cells overexpressing N17-Ras presented lower levels of apoptosis when maintained in SF-medium. On the other hand, transient transfection of a dominant-negative Raf-1 construct (K375W-Raf-1) did not decrease apoptosis; slightly increasing DNA fragmentation levels were seen. Similar results were obtained when the cells were incubated in the presence of a MEK1 inhibitor. The results p...Continue Reading

Citations

May 13, 1999·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·L P WengQ Yu
Dec 22, 2015·Apoptosis : an International Journal on Programmed Cell Death·Eltyeb AbdelwahidGabor Foldes
Mar 20, 2009·Molecular Medicine·Anastasia StavropoulouMichael Koutsilieris
May 16, 2007·Journal of Cellular Physiology·Sebastien AntherieuRoger Rahmani
Dec 20, 2011·Nature Cell Biology·Kathryn AustgenScott A Oakes
Jan 3, 2001·The Journal of Cell Biology·J J SmithS Kornbluth
Feb 13, 2002·Molecular and Cellular Biology·Jesse J SmithSally Kornbluth
Sep 29, 2004·Cellular Signalling·Aleksandra Ellert-MiklaszewskaLiliana Konarska

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis