PIMT Binding to C-Terminal Ala459 of CAIX Is Involved in Inside-Out Signaling Necessary for Its Catalytic Activity

International Journal of Molecular Sciences
Veronika SimkoJaromir Pastorek

Abstract

Human carbonic anhydrase IX (CAIX), a unique member of the α carbonic anhydrase family, is a transmembrane glycoprotein with high enzymatic activity by which CAIX contributes to tumorigenesis through pH regulation. Due to its aberrant expression, CAIX is considered to be a marker of tumor hypoxia and a poor prognostic factor of several human cancers. Hypoxia-activated catalytic function of CAIX is dependent on posttranslational modification of its short intracellular domain. In this work, we have identified that C-terminal Ala459 residue, which is common across CAIX of various species as well as additional transmembrane isoforms, plays an important role in CAIX activation and in pH regulation. Moreover, structure prediction I-TASSER analysis revealed involvement of Ala459 in potential ligand binding. Using tandem mass spectrometry, Protein-L-isoaspartyl methyltransferase (PIMT) was identified as a novel interacting partner, further confirmed by an in vitro pulldown assay and an in situ proximity ligation assay. Indeed, suppression of PIMT led to increased alkalinization of culture media of C33a cells constitutively expressing CAIX in hypoxia. We suggest that binding of PIMT represents a novel intracellular signal required for e...Continue Reading

References

Jun 1, 1976·Journal of Neurochemistry·E J Diliberto, J Axelrod
Jan 1, 1995·Annual Review of Biochemistry·W S Sly, P Y Hu
Nov 15, 1996·Archives of Biochemistry and Biophysics·C G DeVryS Clarke
Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·E KimS G Young
Apr 29, 1998·Archives of Biochemistry and Biophysics·R R Desrosiers, R Béliveau
Aug 29, 2003·Cellular and Molecular Life Sciences : CMLS·K J Reissner, D W Aswad
Sep 18, 2003·Nature Reviews. Cancer·Gregg L Semenza
Apr 19, 2005·Biochimica Et Biophysica Acta·Juraj KopacekSilvia Pastorekova
Nov 1, 2005·Molecular Genetics and Metabolism·Huiping ZhuRichard H Finnell
Nov 29, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Thambi DoraiJanice P Dutcher
Jul 27, 2007·American Journal of Physiology. Cell Physiology·Patricio E MorganJoseph R Casey
Jan 31, 2012·International Journal of Cancer. Journal International Du Cancer·Akiko HoriuchiIkuo Konishi
Jun 28, 2012·Nature Communications·Jae-Cheol LeeJeung-Whan Han
Oct 9, 2013·Frontiers in Physiology·Lucia CsaderovaEliska Svastova
Aug 15, 2014·Seminars in Cancer Biology·Jaromir Pastorek, Silvia Pastorekova
Sep 14, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xiaoyan XuanPingping Liu
Dec 31, 2014·Nature Methods·Jianyi YangYang Zhang
Apr 18, 2015·Nucleic Acids Research·Jianyi Yang, Yang Zhang

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Methods Mentioned

BETA
fluorescence microscopy
deamidation
pull-down
proximity ligation
PCR
transfection
protein assay
FCS
confocal microscopy

Software Mentioned

TASSER
Cytosoft
ImageJ
TASSER ( Threading ASSEmbly Refinement )
ProteinLynx Global Server
Gene Expression Profiling Interactive Analysis ( GEPIA )
Axiovision
ProteinCenter
MatInspector

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