HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 6, 3816-3824, February 7, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/6/3816    most recent M209404200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Andersson, K. B. Articles by Gabrielsen, O. S. Search for Related Content PubMed PubMed Citation Articles by Andersson, K. B. Articles by Gabrielsen, O. S. Social Bookmarking                      What's this?

Phosphorylation-dependent Down-regulation of c-Myb DNA Binding Is Abrogated by a Point Mutation in the v-myb Oncogene^*

Kristin Brevik Andersson^§¶, Elisabeth Kowenz-Leutz^¶, Elen Margrethe Brendeford, Ann-Helen Herwig Tygsett, Achim Leutz, and Odd S. Gabrielsen^**

From the  Department of Biochemistry, University of Oslo, N-0316 Oslo, Norway and the  Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13092 Berlin, Germany

The viral Myb (v-Myb) oncoprotein of the avian myeloblastosis virus (AMV) is an activated form of the cellular transcription factor c-Myb causing acute monoblastic leukemia in chicken. Oncogenic v-Myb alterations include N- and C-terminal deletions as well as point mutations. Whereas truncations in Myb cause loss of various protein modifications, none of the point mutations in v-Myb has been directly linked to protein modifications. Here we show that the DNA-binding domain of c-Myb can be phosphorylated on serine 116 by the catalytic subunit of protein kinase A. Phosphorylation of Ser¹¹⁶ differentially destabilizes a subtype of c-Myb-DNA complexes. The V117D mutation of the AMV v-Myb oncoprotein abolishes phosphorylation of the adjacent Ser¹¹⁶ residue. Modification of Ser¹¹⁶ was also detected in live cells in c-Myb, but not in AMV v-Myb. Phosphorylation-mimicking mutants of c-Myb failed to activate the resident mim-1 gene. Our data imply that protein kinase A or a kinase with similar specificity negatively regulates c-Myb function, including collaboration with C/EBP, and that the leukemogenic AMV v-Myb version evades inactivation by a point mutation that abolishes a phosphoacceptor consensus site. This suggests a novel link between Myb, a signal transduction pathway, cooperativity with C/EBP, and a point mutation in the myb oncogene.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				F. Fang, M. A. Rycyzyn, and C. V. Clevenger Role of c-Myb during Prolactin-Induced Signal Transducer and Activator of Transcription 5a Signaling in Breast Cancer Cells Endocrinology, April 1, 2009; 150(4): 1597 - 1606. [Abstract] [Full Text] [PDF]

				P. K. Purbey, S. Singh, D. Notani, P. P. Kumar, A. S. Limaye, and S. Galande Acetylation-Dependent Interaction of SATB1 and CtBP1 Mediates Transcriptional Repression by SATB1 Mol. Cell. Biol., March 1, 2009; 29(5): 1321 - 1337. [Abstract] [Full Text] [PDF]

				T. Saether, T. Berge, M. Ledsaak, V. Matre, A. H. Alm-Kristiansen, O. Dahle, F. Aubry, and O. S. Gabrielsen The Chromatin Remodeling Factor Mi-2{alpha} Acts as a Novel Co-activator for Human c-Myb J. Biol. Chem., May 11, 2007; 282(19): 13994 - 14005. [Abstract] [Full Text] [PDF]

				M. Fukuzawa, N. V. Zhukovskaya, Y. Yamada, T. Araki, and J. G. Williams Regulation of Dictyostelium prestalk-specific gene expression by a SHAQKY family MYB transcription factor Development, May 1, 2006; 133(9): 1715 - 1724. [Abstract] [Full Text] [PDF]