Abstract
Recent evidence supports the presence of an L-glutamyl methyltransferase(s) in eukaryotic cells, but this enzyme class has been defined only in certain prokaryotic species. Here, we characterize the human C6orf211 gene product as "acidic residue methyltransferase-1" (Armt1), an enzyme that specifically targets proliferating cell nuclear antigen (PCNA) in breast cancer cells, predominately methylating glutamate side chains. Armt1 homologs share structural similarities with the SAM-dependent methyltransferases, and negative regulation of activity by automethylation indicates a means for cellular control. Notably, shRNA-based knockdown of Armt1 expression in two breast cancer cell lines altered survival in response to genotoxic stress. Increased sensitivity to UV, adriamycin, and MMS was observed in SK-Br-3 cells, while in contrast, increased resistance to these agents was observed in MCF7 cells. Together, these results lay the foundation for defining the mechanism by which this post-translational modification operates in the DNA damage response (DDR).
References
Aug 15, 1976·Experientia·S Kim, W K Paik
Dec 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·I B RunnebaumS Sukumar
Apr 15, 1997·Structure·S Djordjevic, A M Stock
May 23, 1998·The Journal of Biological Chemistry·R U JänickeA G Porter
Oct 13, 2001·Molecular Biology of the Cell·A P GaschP O Brown
Jul 18, 2002·The Journal of Biological Chemistry·Mikhail N Levit, Jeffry B Stock
Sep 13, 2002·Nature·Carsten HoegeStefan Jentsch
Dec 31, 2002·Current Opinion in Structural Biology·Jennifer L Martin, Fiona M McMillan
Mar 28, 2003·The EMBO Journal·Yehudit BirgerMichael Bustin
Jun 27, 2003·Trends in Biochemical Sciences·Heidi L SchubertXiaodong Cheng
Sep 12, 2003·Nature·Philipp Stelter, Helle D Ulrich
Jun 3, 2004·Electrophoresis·Giovanni CandianoPier Giorgio Righetti
Apr 20, 2005·Amino Acids·M A Grillo, S Colombatto
Aug 5, 2006·Proteomics·Derek J HoelzLinda H Malkas
Nov 23, 2006·Nature Cell Biology·Shao-Chun WangMien-Chie Hung
May 22, 2007·Cell·George-Lucian MoldovanStefan Jentsch
Dec 19, 2007·PLoS Genetics·David AlvaroRodney Rothstein
Jan 25, 2008·BMC Bioinformatics·Yang Zhang
Jan 29, 2008·Journal of Proteome Research·Robert SprungYingming Zhao
Mar 5, 2009·Microbiology and Molecular Biology Reviews : MMBR·Lauren S WatersGraham C Walker
May 16, 2009·Biochemical Society Transactions·Ivaylo Stoimenov, Thomas Helleday
Sep 2, 2009·Biochemical and Biophysical Research Communications·Adam LesnerMalgorzata Simm
Feb 5, 2011·Molecular Cell·Vitali StanevichYongna Xing
May 5, 2011·Blood·Dong Hwan Dennis KimJeffrey H Lipton
May 10, 2011·PLoS Genetics·Anita K DunbierMitch Dowsett
Dec 27, 2011·Molecular Cell·Jing YangDavid Barford
Citations
Mar 2, 2016·Nature Genetics·Alison M DunningStacey L Edwards
Jun 17, 2015·Journal of Proteomics·Yih-Huei UenChing-Yu Lin
Jun 21, 2016·Nature Chemical Biology·Lili HuangAndrew D Hanson
Dec 10, 2016·Scientific Reports·Yi-Ru LeeNei-Li Chan
Jan 11, 2017·The Journal of Cell Biology·Bradlee NelmsWayne Lencer
Jun 28, 2017·PloS One·Rajendra MandageGabriel Santpere
Oct 13, 2018·Transfusion·Julie A ReiszAngelo D'Alessandro
Jun 28, 2020·Hormones & Cancer·David K LungElaine T Alarid
Jan 16, 2019·Breast Cancer Research : BCR·Joshua HoffmanElad Ziv
Oct 10, 2015·Oncotarget·Derek Hoelz
Jul 19, 2020·Journal of Structural Biology·Taylor N DennisJ Jefferson P Perry