P53 suppresses ribonucleotide reductase via inhibiting mTORC1

Oncotarget
Zhengfu HeChangxian Shen

Abstract

Balanced deoxyribonucleotides pools are essential for cell survival and genome stability. Ribonucleotide reductase is the rate-limiting enzyme for the production of deoxyribonucleotides. We report here that p53 suppresses ribonucleotide reductase subunit 1 (RRM1) and 2 (RRM2) via inhibiting mammalian target of rapamycin complex 1 (mTORC1). In vitro, cancer cell lines and mouse embryonic fibroblast cells were treated with different concentrations of pharmacological inhibitors for different times. In vivo, rhabdomyosarcoma Rh30 cell tumor-bearing mice were treated with rapamycin or AZD8055. Protein levels and phosphorylation status were assessed by immunoblotting and mRNA levels were determined by real time RT-PCR. Pharmacological inhibition of mTORC1 with rapamycin, mTOR kinase with AZD8055 or protein kinase B with MK2206 resulted in decrease of RRM1 and RRM2 in Rh30 cells both in vitro and in mouse tumor xenografts. Moreover, eukaryotic translational initiation factor 4E-binding proteins 1 and 2 double knockout mouse embryonic fibroblast cells demonstrated an elevation of RRM1 and RRM2. Furthermore, down-regulation of mTOR-protein kinase B signaling or cyclin dependent kinase 4 led to decrease of RRM1 and RRM2 mRNAs. In additio...Continue Reading

References

Nov 9, 1994·Molecular and Cellular Biochemistry·T W Traut
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Xiaolan Zhao, Rodney Rothstein
Aug 3, 2002·Genes & Development·Satya Prakash, Louise Prakash
May 4, 2004·Nature Reviews. Cancer·Mary-Ann Bjornsti, Peter J Houghton
Dec 13, 2005·Nature Reviews. Drug Discovery·Bryan T HennessyGordon B Mills
Feb 3, 2006·Genes & Development·Yang David Lee, Stephen J Elledge
Feb 14, 2006·Cell·Stephan WullschlegerMichael N Hall
May 26, 2006·Nature·Reuben J Shaw, Lewis C Cantley
Jun 8, 2006·Annual Review of Biochemistry·Pär Nordlund, Peter Reichard
Jul 4, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christopher K Mathews
Mar 24, 2007·Nature Reviews. Molecular Cell Biology·Karen H Vousden, David P Lane
Aug 19, 2007·Molecular and Cellular Biology·Changxian ShenMary-Ann Bjornsti
Feb 15, 2008·Nature Reviews. Cancer·Robert G Bristow, Richard P Hill
Oct 15, 2008·Molecular Cell·Yang David LeeStephen J Elledge
Apr 20, 2010·Trends in Cell Biology·Zhaohui Feng, Arnold J Levine
Oct 23, 2010·Molecular Cell·Shomit SenguptaDavid M Sabatini
Oct 23, 2010·Molecular Cell·Kathryn E Wellen, Craig B Thompson
Dec 16, 2010·Nature Reviews. Molecular Cell Biology·Roberto ZoncuDavid M Sabatini
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Nov 22, 2011·Pediatric Blood & Cancer·Richard GorlickMalcolm A Smith
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
Jul 3, 2013·Proceedings of the National Academy of Sciences of the United States of America·Changxian Shen, Peter J Houghton
Jun 15, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christopher K Mathews
Sep 20, 2015·Nucleic Acids Research·Martin FischerKurt Engeland
Apr 25, 2016·Neoplasia : an International Journal for Oncology Research·Felix Y FengDaniel A Hamstra

❮ Previous
Next ❯

Citations

Jan 10, 2019·Journal of Attention Disorders·Lena GrünewaldAndreas Reif
Dec 1, 2018·Journal of Molecular Cell Biology·Juan LiuZhaohui Feng
Mar 12, 2021·Cell Cycle·Zhengfu HeChangxian Shen
Apr 1, 2021·Seminars in Cancer Biology·Yanqing Liu, Wei Gu
Jan 30, 2021·Cancer Research·Guillaume RieunierValentine M Macaulay
May 6, 2021·Cell Reports Medicine·Rossana ApriglianoBarbara van Loon
May 18, 2021·Frontiers in Oncology·Jieling LiShaoxiang Wang

❮ Previous
Next ❯

Methods Mentioned

BETA
xenografts
xenograft
PCR
transfection

Software Mentioned

GraphPad Prism

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.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Changxian Shen, P J Houghton
Proceedings of the National Academy of Sciences of the United States of America
Ola LarssonNahum Sonenberg
© 2022 Meta ULC. All rights reserved