The Human Papillomavirus E6 PDZ Binding Motif Links DNA Damage Response Signaling to E6 Inhibition of p53 Transcriptional Activity

Journal of Virology
Jayashree ThatteLawrence Banks

Abstract

The presence of a PDZ binding motif (PBM) in the human papillomavirus (HPV) E6 oncoprotein appears to be a characteristic marker of high oncogenic potential and confers interaction with a number of different cellular PDZ domain-containing substrates. The E6 PBM is also subject to phosphorylation, resulting in inhibition of E6 PDZ binding activity and instead allowing E6 to associate with 14-3-3 proteins. In this study, we analyzed the conditions under which the E6 PBM is phosphorylated. We demonstrate that in normal cycling cells, the levels of E6 phosphorylation are very low. However, following exposure of cells to oxidative stress or the induction of DNA damage, there is a striking increase in the levels of E6 phosphorylation. Depending on the specific stimulus, this phosphorylation of E6 can involve the ATM/ATR pathway and is performed primarily through Chk1, although the Chk2 pathway is also involved indirectly through activation of protein kinase A (PKA). To understand the biological relevance of these phospho-modifications of E6, we analyzed their effects upon the ability of E6 to inhibit p53 transcriptional activity. We show that an intact E6 phospho-acceptor site plays an essential role in the ability of E6 to inhibit p...Continue Reading

References

Jun 24, 1997·Proceedings of the National Academy of Sciences of the United States of America·S S LeeR T Javier
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·T KiyonoM Ishibashi
Nov 6, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mitsuo YoshinouchiKenji Yamato
Aug 3, 2005·Proceedings of the National Academy of Sciences of the United States of America·Kyung-Won HuhKarl Münger
May 16, 2006·Seminars in Cancer Biology·Mong-Hong Lee, Guillermina Lozano
Apr 25, 2007·Oncogene·P SekaricE J Androphy
Dec 20, 2007·Cancer Research·W Brian DaltonVincent W Yang
Sep 25, 2008·Nucleic Acids Research·Sridharan RajagopalanAlan R Fersht
Nov 26, 2009·Nucleic Acids Research·Sridharan RajagopalanAlan R Fersht
Jan 8, 2010·Molecular Biology of the Cell·Mary E GagouMark Meuth
May 17, 2011·FEBS Letters·Ariel BensimonYosef Shiloh
Aug 26, 2011·DNA Repair·Serah ChoiChristopher J Bakkenist
Dec 16, 2011·Molecular Biology of the Cell·James D OrthTimothy J Mitchison
Sep 14, 2012·FEBS Letters·Morten P OksvoldErlend B Smeland
Nov 24, 2012·Nature Reviews. Cancer·Lawrence BanksMiranda Thomas
Dec 5, 2012·Vaccine·John DoorbarMargaret A Stanley
Jul 12, 2013·The Journal of Biological Chemistry·Chun-Ling DaiCheng-Xin Gong

❮ Previous
Next ❯

Citations

Feb 28, 2019·The Journal of General Virology·Vanessa Sarabia-Vega, Lawrence Banks
Oct 18, 2018·Nature Communications·Marianna MadeoPaola D Vermeer
Dec 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jeongkwan HongHyunju Ro
Mar 16, 2021·Tumour Virus Research·Arushi VatsLawrence Banks

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.