Protein phosphatase 2A regulatory subunit B56alpha associates with c-myc and negatively regulates c-myc accumulation

Molecular and Cellular Biology
Hugh K Arnold, R Sears

Abstract

Protein phosphatase 2A (PP2A) plays a prominent role in controlling accumulation of the proto-oncoprotein c-Myc. PP2A mediates its effects on c-Myc by dephosphorylating a conserved residue that normally stabilizes c-Myc, and in this way, PP2A enhances c-Myc ubiquitin-mediated degradation. Stringent regulation of c-Myc levels is essential for normal cell function, as c-Myc overexpression can lead to cell transformation. Conversely, PP2A has tumor suppressor activity. Uncovering relevant PP2A holoenzymes for a particular target has been limited by the fact that cellular PP2A represents a large heterogeneous population of trimeric holoenzymes, composed of a conserved catalytic subunit and a structural subunit along with a variable regulatory subunit which directs the holoenzyme to a specific target. We now report the identification of a specific PP2A regulatory subunit, B56alpha, that selectively associates with the N terminus of c-Myc. B56alpha directs intact PP2A holoenzymes to c-Myc, resulting in a dramatic reduction in c-Myc levels. Inhibition of PP2A-B56alpha holoenzymes, using small hairpin RNA to knock down B56alpha, results in c-Myc overexpression, elevated levels of c-Myc serine 62 phosphorylation, and increased c-Myc fun...Continue Reading

References

Apr 3, 1992·Cell·G I EvanD C Hancock
Aug 1, 1991·Molecular and Cellular Biology·R RuedigerG Walter
Apr 1, 1991·Molecular and Cellular Biology·S I YangM C Mumby
Jan 1, 1986·Annual Review of Genetics·M D Cole
Dec 1, 1987·Molecular and Cellular Biology·T R Jones, M D Cole
Nov 3, 1995·The Journal of Biological Chemistry·B McCright, D M Virshup
Nov 1, 1996·Molecular and Cellular Biology·K OkamotoD Beach
Oct 15, 1998·Proceedings of the National Academy of Sciences of the United States of America·J GötzW Kues
Mar 17, 1999·Molecular Cell·R SearsJ R Nevins
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·R ShtrichmanT Kleinberger
Sep 17, 1999·Molecular Cell·D W Felsher, J M Bishop
Dec 2, 1999·Experimental Cell Research·C V DangK Zeller

❮ Previous
Next ❯

Citations

Jan 25, 2008·Cancer Metastasis Reviews·Anna A Sablina, William C Hahn
Jan 24, 2008·Cancer Metastasis Reviews·Danilo Perrotti, Paolo Neviani
Nov 22, 2011·Neurochemical Research·Rao Muralikrishna AdibhatlaA Gusain
Aug 9, 2013·Medical Oncology·Tuomo RantanenNiku Oksala
Feb 12, 2010·Molecular Neurobiology·Rao Muralikrishna Adibhatla, James F Hatcher
Jan 27, 2010·Oncogene·W C Gustafson, W A Weiss
Dec 3, 2009·The Journal of Biological Chemistry·Pekka T HeikkinenPanu M Jaakkola
Dec 17, 2009·The Journal of Biological Chemistry·Julienne R Escamilla-PowersRosalie Sears
Oct 27, 2010·The Journal of Biological Chemistry·Simone BuraschiRenato V Iozzo
Jun 29, 2011·The Journal of Biological Chemistry·Aneta DobierzewskaMariana N Nikolova-Karakashian
Dec 29, 2006·The Journal of Biological Chemistry·Julienne R Escamilla-Powers, Rosalie C Sears
Nov 26, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Archana MukhopadhyayBesim Ogretmen
Oct 17, 2009·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Bryan M Turner
Mar 21, 2009·Molecular Pharmacology·Jamie L McConnell, Brian E Wadzinski
Jul 26, 2008·Journal of Virology·Haggit Ben-IsraelTamar Kleinberger
May 30, 2013·Molecular and Cellular Biology·Amy S FarrellRosalie C Sears
Jan 27, 2011·Cancer Research·Xiaoyan WangRosalie C Sears
Dec 17, 2010·Cancer Research·Anna A SablinaWilliam C Hahn
Nov 12, 2009·Molecular Cancer Research : MCR·Jinfeng ZhaoXingming Deng
Jul 23, 2011·Genes & Cancer·Jinhua XuOlufunmilayo I Olopade
Apr 7, 2011·Experimental & Molecular Medicine·Chang Hoon Cho
Jan 10, 2014·The Journal of Clinical Investigation·Alejandro GutierrezJon C Aster
Apr 29, 2014·Cell Death and Differentiation·B WangX Deng
Dec 7, 2007·Proceedings of the National Academy of Sciences of the United States of America·Craig M ForesterDavid M Virshup
Jun 14, 2014·Proceedings of the National Academy of Sciences of the United States of America·Mahnaz JanghorbanRosalie C Sears
May 8, 2015·International Journal of Molecular Sciences·Lauren M SommerJoni M Seeling
Apr 4, 2015·Cancer Biology & Therapy·Annalisa FicoEmilia Caputo
Jan 10, 2009·The EMBO Journal·Hugh K ArnoldRosalie C Sears
Nov 29, 2011·Enzyme Research·Qingxiu Zhang, Francois X Claret
Apr 20, 2016·Frontiers in Oncology·Elena ArriazuMaría D Odero
Sep 13, 2013·Cancer Biology & Therapy·Archana MukhopadhyayJane V Aldrich

❮ 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.