Aneugenic activity of Op18/stathmin is potentiated by the somatic Q18-->e mutation in leukemic cells.

Molecular Biology of the Cell
Per HolmfeldtMartin Gullberg

Abstract

Op18/stathmin (Op18) is a phosphorylation-regulated microtubule destabilizer that is frequently overexpressed in tumors. The importance of Op18 in malignancy was recently suggested by identification of a somatic Q18-->E mutation of Op18 in an adenocarcinoma. We addressed the functional consequences of aberrant Op18 expression in leukemias by analyzing the cell cycle of K562 cells either depleted of Op18 by expression of interfering hairpin RNA or induced to express wild-type or Q18E substituted Op18. We show here that although Op18 depletion increases microtubule density during interphase, the density of mitotic spindles is essentially unaltered and cells divide normally. This is consistent with phosphorylation-inactivation of Op18 during mitosis. Overexpression of wild-type Op18 results in aneugenic activities, manifest as aberrant mitosis, polyploidization, and chromosome loss. One particularly significant finding was that the aneugenic activity of Op18 was dramatically increased by the Q18-->E mutation. The hyperactivity of mutant Op18 is apparent in its unphosphorylated state, and this mutation also suppresses phosphorylation-inactivation of the microtubule-destabilizing activity of Op18 without any apparent effect on its p...Continue Reading

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Citations

Jan 30, 2010·The Journal of Biological Chemistry·Po-Wen ChenChing-Hwa Tsai
Apr 11, 2009·The Journal of Biological Chemistry·Tapas MannaLeslie Wilson
Mar 9, 2007·Molecular Biology of the Cell·Per HolmfeldtMartin Gullberg
Apr 25, 2008·Molecular Biology of the Cell·Mikael E SellinMartin Gullberg
Jun 12, 2009·Molecular Biology of the Cell·Danielle N Ringhoff, Lynne Cassimeris
Oct 3, 2012·PloS One·Sara D'AndreaGustavo Baldassarre
Jul 9, 2009·Cellular and Molecular Life Sciences : CMLS·Per HolmfeldtMartin Gullberg
Oct 8, 2011·Expert Opinion on Therapeutic Targets·Barbara Belletti, Gustavo Baldassarre
Sep 2, 2008·Expert Review of Anticancer Therapy·Shushan RanaJohn Nemunaitis
Dec 13, 2007·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Aug 16, 2014·Asian Pacific Journal of Cancer Prevention : APJCP·Joao Agostinho Machado-Neto
Nov 28, 2021·Investigational New Drugs·Hugo Passos VicariJoão Agostinho Machado-Neto

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