Copine-I represses NF-kappaB transcription by endoproteolysis of p65

Oncogene
C S RamseyM W Mayo

Abstract

Nuclear factor-kappaB (NF-kappaB) is a dynamic transcription factor that regulates important biological processes involved in cancer initiation and progression. Identifying regulators that control the half-life of NF-kappaB is important to understanding molecular processes that control the duration of transcriptional responses. In this study we identify copine-I, a calcium phospholipid-binding protein, as a novel repressor that physically interacts with p65 to inhibit NF-kappaB transcription. Knockdown of copine-I by siRNA increases tumor necrosis factor alpha-stimulated NF-kappaB transcription, while copine-I expression blocks endogenous transcription. Copine-I abolishes NF-kappaB transcription by inducing endoprotease processing of the N-terminus of p65, a process antagonized by IkappaB alpha. Copine-I stimulates endoproteolysis of p65 within a conserved region that is required for base-specific contact with DNA. p65 proteins lacking the N-terminus fail to bind to DNA and act as dominant-negative molecules that inhibit NF-kappaB transcription. Our work provides evidence that copine-I regulates the half-life of NF-kappaB transcriptional responses through a novel mechanism that involves endoproteolysis of the p65 protein.

References

Jan 1, 1996·Annual Review of Immunology·A S Baldwin
Dec 1, 1996·Protein Science : a Publication of the Protein Society·E A Nalefski, J J Falke
Jan 23, 1998·Nature Structural Biology·Y Q ChenG Ghosh
Jun 20, 1998·The Journal of Biological Chemistry·J Rizo, T C Südhof
Jul 24, 1998·Cellular and Molecular Life Sciences : CMLS·S K Dickeson, S A Santoro
Dec 29, 1998·Cell·M D Jacobs, S C Harrison
May 29, 2000·The Journal of Biological Chemistry·C B PhelpsG Ghosh
Jun 3, 2000·Annual Review of Immunology·M Karin, Y Ben-Neriah
Oct 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S KurosawaD J Stearns-Kurosawa
Oct 9, 2002·The American Journal of Pathology·Katherine S WilsonJoseph Geradts
Nov 21, 2002·Cellular and Molecular Life Sciences : CMLS·J L Tomsig, C E Creutz
Apr 3, 2003·Biochemical and Biophysical Research Communications·Rangan MaitraByungkook Lee
May 16, 2003·Lancet·Erich HuangAndrew T Huang
Dec 17, 2003·The Biochemical Journal·Jose Luis TomsigCarl E Creutz
Jan 6, 2004·Science·Siming LiMarc Vidal
Jul 1, 2004·The Journal of Experimental Medicine·Simona SaccaniGioacchino Natoli
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh
Apr 1, 2005·The Journal of Biological Chemistry·Ezra BursteinColin S Duckett
Sep 2, 2005·Molecular and Cellular Biology·Lin-Feng ChenWarner C Greene
Sep 22, 2005·Nature Reviews. Immunology·Michael Karin, Florian R Greten
Dec 31, 2005·Molecular and Cellular Biology·Jamie E HobergMarty W Mayo

❮ Previous
Next ❯

Citations

Dec 25, 2012·Molecules and Cells·Nammi ParkJae-Yong Park
Dec 21, 2010·Oncogene·M M ChaturvediB B Aggarwal
Oct 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·David F AllisonMarty W Mayo
Apr 3, 2009·Genes & Development·Xicheng MaoEzra Burstein
Sep 29, 2011·Development, Growth & Differentiation·Kerry A FlegelCynthia K Damer
Nov 23, 2010·The FEBS Journal·Pavel V PerestenkoRobert Andrew Jeffrey McIlhinney
Oct 28, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·Ru ChenTeresa A Brentnall
Jul 3, 2019·International Journal of Cancer. Journal International Du Cancer·Xiang ShuWei Zheng
Jan 20, 2016·Oncology Reports·N Monique ParicharttanakulJisnuson Svasti
Feb 20, 2021·The Journal of Trauma and Acute Care Surgery·Zhiwei WangTianbing Wang
Aug 10, 2021·Frontiers in Genetics·Haicheng TangFeng Li

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.