Synergy between the Mos/mitogen-activated protein kinase pathway and loss of p53 function in transformation and chromosome instability.

Molecular and Cellular Biology
K Fukasawa, G F Vande Woude

Abstract

Constitutive activation of mitogen-activated protein kinase (MAPK) is a property common to many oncoproteins, including Mos, Ras, and Raf, and is essential for their transforming activities. We have shown that high levels of expression of the Mos/MAPK pathway in Swiss 3T3 fibroblast cause cells in S phase to undergo apoptosis, while cells in G1 irreversibly growth arrest. Interestingly, cells in G2 and M phases also arrest at a G1-like checkpoint after proceeding through mitosis. These cells fail to undergo cytokinesis and are binucleated. Thus, constitutive overexpression of Mos and MAPK cannot be tolerated, and fibroblasts transformed by Mos express only low levels of the mos oncogene product. Here, we show that p53 plays a key role in preventing oncogene-mediated activation of MAPK. In the absence of p53 (p53-/-), the growth arrest normally observed in wild-type p53 (p53+/+) mouse embryo fibroblasts (MEFs) is markedly reduced. The mos transformation efficiency in p53-/- MEFs is two to three orders of magnitude higher than that in p53+/+ cells, and p53-/- cells tolerate > 10-fold higher levels of both Mos and activated MAPK. Moreover, we show that, like Mos, both v-ras and v-raf oncogene products induce apoptosis in p53+/+ ME...Continue Reading

References

Jul 30, 1992·Nature·J M KyriakisJ Avruch
Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·C GallegoG L Johnson
Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S J KuerbitzM B Kastan
Oct 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·E K ShibuyaJ V Ruderman
Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·D J RobbinsM H Cobb
Jul 1, 1991·Molecular and Cellular Biology·K FukasawaS Chen
Jul 5, 1991·Science·M HollsteinC C Harris
Oct 17, 1991·Nature·B J PulvererJ R Woodgett
Mar 1, 1991·Molecular and Cellular Biology·G G HicksM Mowat
Aug 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·W E MercerS J Ullrich
Nov 1, 1990·Molecular and Cellular Biology·L DillerB Vogelstein
Aug 1, 1986·Journal of Virology·J W YewdellD P Lane
Nov 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·D EliyahuM Oren
Sep 1, 1971·The Journal of Pathology·J F Kerr
Apr 1, 1973·Virology·F L Graham, A J van der Eb
Jun 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·D G BlairG F Vande Woude
Mar 1, 1995·Cancer Metastasis Reviews·M B KastanC J Leonard
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·M L AgarwalG R Stark
Apr 11, 1995·Proceedings of the National Academy of Sciences of the United States of America·K Fukasawa, G F Vande Woude

❮ Previous
Next ❯

Citations

Jan 5, 2001·Expert Opinion on Investigational Drugs·Y KloogM Sinensky
Jan 19, 2010·Journal of Cellular Biochemistry·Jean-François L Bodart
May 4, 2005·Biochemical and Biophysical Research Communications·Anette Duensing, Stefan Duensing
Aug 23, 2005·Biochimica Et Biophysica Acta·Patrizio Castagnola, Walter Giaretti
Oct 17, 1998·Toxicology and Applied Pharmacology·M GekleH Schramek
Feb 28, 2002·Current Biology : CB·Andrei KhokhlatchevJoseph Avruch
May 3, 2003·Cancer Cell·Harold I SaavedraGustavo Leone
Aug 17, 1999·Seminars in Cancer Biology·G A Pihan, S J Doxsey
Nov 10, 2006·Cancer Cell International·Rengaswami RajaramanSelva R Rajaraman
Sep 4, 1999·Journal of Applied Microbiology·N S Duesbery, G F Vande Woude
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·J H WrightE G Krebs
Mar 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·N S DuesberyG F Vande Woude
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·D W Felsher, J M Bishop
Jun 29, 2004·Nature Cell Biology·Xiaolong YangTian Xu
Sep 2, 1999·International Journal of Cancer. Journal International Du Cancer·M V Blagosklonny, T Fojo
Oct 18, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Sujoy BhattacharyaLeonard R Johnson
Apr 16, 2004·International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists·Wei-Cheng XueAnnie N Y Cheung
Aug 5, 2017·Journal of Cellular Physiology·Antonella MuscellaSanto Marsigliante
Jun 22, 2001·Leukemia·M V Blagosklonny
Nov 24, 2007·Cancer Chemotherapy and Pharmacology·Saska MarcziMladen Zinić
May 13, 1999·Molecular Neurobiology·G Fulci, E G Van Meir
Feb 27, 2010·The EMBO Journal·Ilio VitaleGuido Kroemer
Nov 15, 2000·Molecular Endocrinology·J M ShirokawaJ A Fagin
Mar 8, 2000·Cancer Investigation·P Tarapore, K Fukasawa
Jan 12, 2012·Cell Communication & Adhesion·George PoulogiannisMark J Arends
Aug 10, 2000·Histopathology·A AthanasiouC Kittas
Nov 7, 1998·The Journal of Biological Chemistry·S BasuR Kolesnick
Feb 7, 1998·The Journal of Biological Chemistry·M L AgarwalG R Stark
Dec 23, 1999·The Journal of Biological Chemistry·H I SaavedraP J Stambrook

❮ Previous
Next ❯

Related Concepts

Related Feeds

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

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.