Inactivation of protein-phosphatase 2A causing hyperphosphorylation of autoantigenic paraprotein targets in MGUS/MM is due to an exchange of its regulatory subunits

International Journal of Cancer

Volumn 135, Issue 9, 2014, Pages 2046-2053

  Preuss, Klaus Dieter ^a   Fadle, Natalie ^a   Regitz, Evi ^a   Held, Gerhard ^a   Pfreundschuh, Michael ^a  

^a SAARLAND UNIVERSITY   (Germany)

Author keywords

autoantigen; B subunit; multiple myeloma; paraprotein; proteinphosphatase 2A

Indexed keywords

AUTOANTIGENIC PARAPROTEIN; CERAMIDE; PARAPROTEIN; PARATARG 7; PHOSPHOPROTEIN PHOSPHATASE 2A; RECOMBINANT PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DEPHOSPHORYLATION; ENZYME ACTIVITY; ENZYME INACTIVATION; ENZYME RECONSTITUTION; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; LYMPHOBLASTOID CELL LINE; MONOCLONAL IMMUNOGLOBULINEMIA; MULTIPLE MYELOMA; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN MODIFICATION; PROTEIN PHOSPHORYLATION; PROTEIN SUBUNIT; PROTEIN TARGETING; WALDENSTROEM MACROGLOBULINEMIA; WILD TYPE;

AUTOANTIGEN; B-SUBUNIT; MULTIPLE MYELOMA; PARAPROTEIN; PROTEINPHOSPHATASE 2A;

APOPTOSIS; AUTOANTIGENS; BLOTTING, WESTERN; CELL PROLIFERATION; CELLS, CULTURED; DNA METHYLATION; ENZYME-LINKED IMMUNOSORBENT ASSAY; HETEROZYGOTE; HUMANS; IMMUNOPRECIPITATION; ISOELECTRIC FOCUSING; MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE; MULTIPLE MYELOMA; PARAPROTEINS; PHOSPHORYLATION; PROTEIN PHOSPHATASE 2; PROTEIN SUBUNITS; RNA, SMALL INTERFERING; WALDENSTROM MACROGLOBULINEMIA;

EID: 84906258905     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.28864     Document Type: Article

References (28)

1. Preuss KD, Pfreundschuh M, Ahlgrimm M, et al. A frequent target of paraproteins in the sera of patients with multiple myeloma and MGUS. Int J Cancer 2009; 125: 656-61.
2. Grass S, Preuss K-D, Ahlgrimm A, et al. Association of a dominantly inherited hyperphosphorylated paraprotein target with sporadic and familial multiple myeloma and monoclonal gammopathy of undetermined significance: a case-control study. Lancet Oncol 2009; 10: 950-6.
3. Grass S, Preuss KD, Wikowicz A, et al. Hyperphosphorylated paratarg-7: a new molecularly defined risk factor for monoclonal gammopathy of undetermined significance of the IgM type and Waldenstrom macroglobulinemia. Blood 2011; 117: 2918-23.
4. Zwick C, Held G, Auth M, et al. Over one-third of African-American MGUS and multiple myeloma patients are carriers of hyperphosphorylated paratarg-7, an autosomal dominantly inherited risk factor for MGUS/MM. Int J Cancer. 2014 Jan 20. doi: 10.1002/ijc.28731. [Epub ahead of print] PubMed PMID: 24443359.
5. Grass S, Preuss K-D, Pfreundschuh M,. Autosomal-dominant inheritance of hyperphosphorylated paratarg-7. Lancet Oncol 2010; 11: 12.
6. Preuss KD, Pfreundschuh M, Fadle N, et al. Hyperphosphorylation of autoantigenic targets of paraproteins is due to inactivation of PP2A2. Blood 2011; 118: 3340-6.
7. Grass S, Preuss KD, Thome S, et al. Paraproteins of familial MGUS/multiple myeloma target family-typical antigens: hyperphosphorylation of autoantigens is a consistent finding in familial and sporadic MGUS/MM. Blood 2011; 118: 635-7.
8. Janssens V, Longin S, Goris J,. PP2A holoenzyme assembly: in cauda venenum (the sting is in the tail). Trends Biochem Sci 2008; 33: 113-21.
9. Janssens V, Goris J,. Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem J 2001; 353 (Part 3): 417-39.
10. Virshup DM, Shenolikar S,. From promiscuity to precision: protein phosphatases get a makeover. Mol Cell 2009; 33: 537-45.
11. Eichhorn PJ, Creyghton MP, Wilhelmsen K, et al. A RNA interference screen identifies the protein phosphatase 2A subunit PR55gamma as a stress-sensitive inhibitor of c-SRC. PLoS Genet 2007; 3: e218.
12. Bornkamm GW, Berens C, Kuklik-Roos C, et al. Stringent doxycycline-dependent control of gene activities using an episomal one-vector system. Nucleic Acids Res 2005; 33: e137.
13. Holzel M, Rohrmoser M, Orban M, et al. Rapid conditional knock-down-knock-in system for mammalian cells. Nucleic Acids Res 2007; 35: e17.
14. Hoet RM, Cohen EH, Kent RB, et al. Generation of high-affinity human antibodies by combining donor-derived and synthetic complementarity-determining- region diversity. Nat Biotechnol 2005; 23: 344-8.
15. Held G, Wadle A, Dauth N, et al. MHC-peptide-specific antibodies reveal inefficient presentation of an HLA-A0201-restricted, Melan-A-derived peptide after active intracellular processing. Eur J Immunol 2007; 37: 2008-17.
16. Mochida S, Ikeo S, Gannon J, et al. Regulated activity of PP2A-B55 delta is crucial for controlling entry into and exit from mitosis in Xenopus egg extracts. EMBO J 2009; 28: 2777-85.
17. Turowski P, Myles T, Hemmings BA, et al. Vimentin dephosphorylation by protein phosphatase 2A is modulated by the targeting subunit B55. Mol Biol Cell 1999; 10: 1997-2015.
18. Gil-Bernabe AM, Romero F, Limon-Mortes MC, et al. Protein phosphatase 2A stabilizes human securin, whose phosphorylated forms are degraded via the SCF ubiquitin ligase. Mol Cell Biol 2006; 26: 4017-27.
19. Dobrowsky RT, Kamibayashi C, Mumby MC, et al. Ceramide activates heterotrimeric protein phosphatase 2A. J Biol Chem 1993; 268: 15523-30.
20. Ruvolo PP, Gao F, Blalock WL, et al. Ceramide regulates protein synthesis by a novel mechanism involving the cellular PKR activator RAX. J Biol Chem 2001; 276: 11754-8.
21. Chen J, Martin BL, Brautigan DL,. Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation. Science 1992; 257: 1261-4.
22. Guo H, Damuni Z,. Autophosphorylation-activated protein kinase phosphorylates and inactivates protein phosphatase 2A. Proc Natl Acad Sci USA 1993; 90: 2500-4.
23. Kyle RA, Rajkumar SV,. Multiple myeloma. N Engl J Med 2004; 351: 1860-73.
24. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893-917.
25. Broderick P, Chubb D, Johnson DC, et al. Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk. Nat Genet 2012; 44: 58-61.
26. Martino A, Campa D, Jamroziak K, et al. Impact of polymorphic variation at 7p15.3, 3p22.1 and 2p23.3 loci on risk of multiple myeloma. I. Br J Haematol 2012; 158: 805-9.
27. Campa D, Martino A, Sainz J, et al. Comprehensive investigation of genetic variation in the 8q24 region and multiple myeloma risk in the IMMEnSE consortium. Br J Haematol 2012; 157: 331-8.
28. Siskind LJ, Kolesnick RN, Colombini M,. Ceramide forms channels in mitochondrial outer membranes at physiologically relevant concentrations. Mitochondrion 2006; 6: 118-25.