SEARCH:   Advanced

Blood, 1 November 2008, Vol. 112, No. 9, pp. 3856-3866. Prepublished online as a Blood First Edition Paper on June 18, 2008; DOI 10.1182/blood-2007-09-111773. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-09-111773v1 112/9/3856    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kawahara, M. Articles by Uchiyama, T. Search for Related Content PubMed PubMed Citation Articles by Kawahara, M. Articles by Uchiyama, T. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Kpm/Lats2 is linked to chemosensitivity of leukemic cells through the stabilization of p73 Masahiro Kawahara1, Toshiyuki Hori1, Kazuhisa Chonabayashi1, Tsutomu Oka2, Marius Sudol2,3, and Takashi Uchiyama1 1 Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 2 Laboratory of Signal Transduction and Proteomic Profiling, Weis Center for Research, Danville, PA; and 3 Department of Medicine, Mount Sinai School of Medicine, New York, NY Down-regulation of the Kpm/Lats2 tumor suppressor is observed in various malignancies and associated with poor prognosis in acute lymphoblastic leukemia. We documented that Kpm/Lats2 was markedly decreased in several leukemias that were highly resistant to conventional chemotherapy. Silencing of Kpm/Lats2 expression in leukemic cells did not change the rate of cell growth but rendered the cells more resistant to DNA damage–inducing agents. Expression of p21 and PUMA was strongly induced by these agents in control cells, despite defective p53, but was only slightly induced in Kpm/Lats2-knockdown cells. DNA damage–induced nuclear accumulation of p73 was clearly observed in control cells but hardly detected in Kpm/Lats2-knockdown cells. Chromatin immunoprecipitation (ChIP) assay showed that p73 was recruited to the PUMA gene promoter in control cells but not in Kpm/Lats2-knockdown cells after DNA damage. The analyses with transient coexpression of Kpm/Lats2, YAP2, and p73 showed that Kpm/Lats2 contributed the stability of YAP2 and p73, which was dependent on the kinase function of Kpm/Lats2 and YAP2 phosphorylation at serine 127. Our results suggest that Kpm/Lats2 is involved in the fate of p73 through the phosphorylation of YAP2 by Kpm/Lats2 and the induction of p73 target genes that underlie chemosensitivity of leukemic cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Lunghi, A. Costanzo, L. Mazzera, V. Rizzoli, M. Levrero, and A. Bonati The p53 Family Protein p73 Provides New Insights into Cancer Chemosensitivity and Targeting Clin. Cancer Res., November 1, 2009; 15(21): 6495 - 6502. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020