{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T14:04:18Z","timestamp":1786889058275,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,4,5]],"date-time":"2014-04-05T00:00:00Z","timestamp":1396656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"DFG (German Research Society)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:p>Hyperphosphorylated paratarg\u20107 (pP\u20107) carrier state is the strongest molecularly defined risk factor for monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM). pP\u20107 is inherited as autosomal\u2010dominant trait and depending on the ethnic background is found in over one\u2010third of MGUS\/MM patients. P\u20107, which is the antigenic paraprotein target in these patients, is hyperphosphorylated at serine<jats:sub>17<\/jats:sub>. P\u20107 hyperphosphorylation can be induced in wild\u2010type P\u20107 (wtP\u20107) carriers by PKC\u03b6 and reverted by protein\u2010phosphatase 2A (PP2A). Here we show that dephosphorylation of pP\u20107 is defective in pP\u20107 carriers due to inactivation of the PP2A by substitution of the regulatory B55\u03b4 subunit with B56\u03b33. In lymphoblastoid cell lines from pP\u20107 carriers, transfection of recombinant B55\u03b4 or treatment with ceramide led to a partial reconstitution of PP2A activity and dephosphorylation of pP\u20107 to wtP7. Similar results were observed with other previously reported autoantigenic paraproteins targets. In conclusion, the mechanisms responsible for the defective dephosphorylation and maintaining the hyperphosphorylated state of P\u20107 and other autoantigenic paraprotein targets have been elucidated, facilitating the identification of the genetic basis underlying this phenomenon which is obviously common in the pathogenesis of MGUS\/MM\/WM and not restricted to pP\u20107 cases.<\/jats:p>","DOI":"10.1002\/ijc.28864","type":"journal-article","created":{"date-parts":[[2014,3,27]],"date-time":"2014-03-27T06:52:45Z","timestamp":1395903165000},"page":"2046-2053","source":"Crossref","is-referenced-by-count":9,"title":["Inactivation of protein\u2010phosphatase 2A causing hyperphosphorylation of autoantigenic paraprotein targets in MGUS\/MM is due to an exchange of its regulatory subunits"],"prefix":"10.1002","volume":"135","author":[{"given":"Klaus\u2010Dieter","family":"Preuss","sequence":"first","affiliation":[{"name":"Jos\u00e9\u2010Carreras\u2010Center for Immuno\u2010 and Gene Therapy 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pfreundschuh","sequence":"additional","affiliation":[{"name":"Jos\u00e9\u2010Carreras\u2010Center for Immuno\u2010 and Gene Therapy Internal Medicine I, Saarland University Medical School Homburg (Saar) Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24427"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70234-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-09-306076"},{"key":"e_1_2_7_5_1","article-title":"Over one\u2010third of African\u2010American MGUS and multiple myeloma patients are carriers of hyperphosphorylated paratarg\u20107, an autosomal dominantly inherited risk factor for MGUS\/MM","author":"Zwick C","journal-title":"Int J 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