PMID: 9653139Jul 8, 1998Paper

Basal and human papillomavirus E6 oncoprotein-induced degradation of Myc proteins by the ubiquitin pathway

Proceedings of the National Academy of Sciences of the United States of America
S Gross-MesilatyA Ciechanover

Abstract

We have previously shown that the degradation of c-myc and N-myc in vitro is mediated by the ubiquitin system. However, the role of the system in targeting the myc proteins in vivo and the identity of the conjugating enzymes and possible ancillary proteins involved has remained obscure. Here we report that the degradation of the myc proteins in cells is inhibited by lactacystin and MG132, two inhibitors of the 20S proteasome. Inhibition is accompanied by accumulation of myc-ubiquitin conjugates. Dissection of the ancillary proteins involved revealed that the high-risk human papillomavirus oncoprotein E6-16 stimulates conjugation and subsequent degradation of the myc proteins in vitro. Expression of E6-16 in cells results in significant shortening of the t1/2 of the myc proteins with subsequent decrease in their cellular level. Analysis of the conjugating enzymes revealed that under basal conditions the proteins can be conjugated by two pairs of E2s and E3s-E2-14 kDa and E3alpha involved in the "N-end rule" pathway, and E2-F1 (UbcH7) and E3-Fos involved also in conjugation of c-Fos. In the presence of E6-16, a third pair, E2-F1 and E6-AP mediate conjugation of myc by means of a mechanism that appears to be similar to that involv...Continue Reading

References

May 29, 1992·Cell·A Varshavsky
Jan 1, 1992·Annual Review of Biochemistry·K B MarcuA J Patel
Apr 3, 1992·Cell·G I EvanD C Hancock
Jan 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·A CiechanoverG M Brodeur
Jan 1, 1991·Advances in Cancer Research·C A Spencer, M Groudine
Dec 1, 1990·Genes & Development·B Lüscher, R N Eisenman
Apr 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·A Hershko, I A Rose
Dec 1, 1986·Molecular and Cellular Biology·G RamsayJ M Bishop
Nov 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·C DaniP Jeanteur
Jan 1, 1996·Annual Review of Genetics·M Hochstrasser
Nov 1, 1996·Trends in Biochemical Sciences·A Hershko
Apr 4, 1997·The Journal of Biological Chemistry·B BercovichA Ciechanover
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·A Ciechanover, A L Schwartz
Jul 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jürgen GentGer J Strous

❮ Previous
Next ❯

Citations

Oct 1, 1965·Journal of Cellular Physiology·A Korner
Sep 28, 2002·International Journal of Cancer. Journal International Du Cancer·Zaroui K MelkoumianJeannine S Strobl
Aug 24, 2001·International Journal of Cancer. Journal International Du Cancer·A Aguilar-LemarroyF Rösl
Feb 10, 2000·Archives of Biochemistry and Biophysics·L ChenJ Bingham Smith
Mar 13, 2001·Biochemical and Biophysical Research Communications·K NoguchiY Kuchino
Jan 21, 2012·Cellular and Molecular Life Sciences : CMLS·Karin HochrainerJosef Anrather
Jul 25, 2006·Archives of Virology·T O Garnett, P J Duerksen-Hughes
Feb 16, 2005·Apoptosis : an International Journal on Programmed Cell Death·Xueli FanJason J Chen
May 22, 2008·Pathology Oncology Research : POR·Ioannis N MammasDemetrios A Spandidos
Jan 22, 2004·Clinica Chimica Acta; International Journal of Clinical Chemistry·Jakub GolabCord Naujokat
Feb 15, 2003·FEBS Letters·Suzanne CamusSonia Lain
Mar 18, 2003·Toxicology and Applied Pharmacology·D S KirkpatrickA J Gandolfi
Mar 19, 2002·Molecular and Biochemical Parasitology·Mariana MatrajtDavid S Roos
May 1, 1999·Trends in Genetics : TIG·C W Greider
Oct 31, 2002·Cancer Letters·Patrick FinzerFrank Rösl
Feb 19, 2000·Current Opinion in Genetics & Development·K Macleod
Nov 25, 2000·Bioorganic & Medicinal Chemistry·W BeerheideA E Ting
Jan 1, 2003·Seminars in Cancer Biology·Nico P Dantuma, Maria G Masucci
Mar 17, 1999·Molecular Cell·R SearsJ R Nevins
Apr 28, 2001·Cytokine & Growth Factor Reviews·A E KoromilasG Matlashewski
Jun 15, 2007·Nature Cell Biology·Nikita PopovMartin Eilers
Jul 4, 2006·Nature Reviews. Drug Discovery·Grzegorz NalepaJ Wade Harper
Jun 4, 2005·Cell Death and Differentiation·M FilippovaP J Duerksen-Hughes
Sep 22, 2006·Viral Immunology·Mingzhou Chen, Denis Gerlier
Jan 10, 2008·Journal of the National Cancer Institute·Marcia Bellon, Christophe Nicot
Jul 28, 2006·Cold Spring Harbor Symposia on Quantitative Biology·D A GallowayJ K McDougall
Jan 29, 2003·Journal of Virology·Lucia G Le Roux, Junona Moroianu
Jul 26, 2002·Molecular and Cellular Biology·Ajay KumarVimla Band

❮ 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