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

J. Biol. Chem., Vol. 278, Issue 44, 42750-42760, October 31, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/44/42750    most recent M307067200v2 M307067200v1 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 Tschan, M. P. Articles by Torbett, B. E. Search for Related Content PubMed PubMed Citation Articles by Tschan, M. P. Articles by Torbett, B. E. Social Bookmarking                      What's this?

Alternative Splicing of the Human Cyclin D-binding Myb-like Protein (hDMP1) Yields a Truncated Protein Isoform That Alters Macrophage Differentiation Patterns^*

Mario P. Tschan, Kimberlee M. Fischer, Vivian S. Fung, Farzaneh Pirnia¶, Markus M. Borner¶||, Martin F. Fey¶||, Andreas Tobler¶**, and Bruce E. Torbett

From the Scripps Research Institute, Department of Molecular and Experimental Medicine, La Jolla, California 92037 and the ^¶Department of Clinical Research, ^||Institute of Medical Oncology, ^**Central Hematology Laboratory, University and Inselspital, Bern, CH-3010, Switzerland

We have cloned two novel, alternatively spliced messages of human cyclin D-binding Myb-like protein (hDMP1). The known, full-length protein has been named hDMP1 and the new isoforms, hDMP1 and hDMP1. The hDMP1, -, and - splice variants have unique expression patterns in normal hematopoietic cells; hDMP1 mRNA transcripts are strongly expressed in quiescent CD34⁺ cells and freshly isolated peripheral blood leukocytes, as compared with hDMP1. In contrast, activated T-cells and developing myeloid cells, macrophages, and granulocytes express low levels of hDMP1 transcripts, and hDMP1 is ubiquitously and weakly expressed. Mouse Dmp1 has been shown to activate CD13/aminopeptidase N (APN) and p19^ARF gene expression via binding to canonical DNA recognition sites in the respective promoters. Assessment of CD13/APN promoter responsiveness demonstrated that hDMP1 but not hDMP1 and -, is a transcriptional activator. Furthermore, hDMP1 was found to inhibit the CD13/APN promoter transactivation ability of hDMP1. Stable, ectopic expression of hDMP1 and, to a lesser extent hDMP1, reduced endogenous cell surface levels of CD13/APN in U937 cells. Moreover, stable, ectopic expression of hDMP1 altered phorbol 12-myristate 13-acetate-induced terminal differentiation of U937 cells to macrophages and resulted in maintenance of proliferation. These results demonstrate that hDMP1 antagonizes hDMP1 activity and suggest that cellular functions of hDMP1 may be regulated by cellular hDMP1 isoform levels.

Received for publication, July 2, 2003 , and in revised form, August 8, 2003.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AF202144 and AF202145.

^* This work was supported in part by National Institutes of Health Grants DK49886 (to B. E. T.), Swiss National Foundation Grant 3100-067213.01/32-53596.98, the Bernese Foundation for Clinical Cancer Research, the Marlies-Schwegler Foundation for Cancer Research, and the Ursula-Hecht-Stiftung for Leukemia Research (to A. T. and M. F. F.). The General Clinical Research Center Normal Blood-drawing Service is funded by National Institutes of Health Grant M01RR00833. This is publication 15453-MEM from The Scripps Research Institute. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of fellowships from the Swiss National Foundation (Grant 84NP-057502), the Swiss Federation against Cancer (Grant BIL OCS-01198-09-2001), and the Bernese Cancer League.

To whom correspondence should be addressed. Tel.: 858-784-9123; Fax: 858-784-7714; E-mail: betorbet{at}scripps.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Jenal, E. Trinh, C. Britschgi, A. Britschgi, V. Roh, S. A. Vorburger, A. Tobler, D. Leprince, M. F. Fey, K. Helin, et al. The Tumor Suppressor Gene Hypermethylated in Cancer 1 Is Transcriptionally Regulated by E2F1 Mol. Cancer Res., June 1, 2009; 7(6): 916 - 922. [Abstract] [Full Text] [PDF]

				K. Inoue, T. Sugiyama, P. Taneja, R. L. Morgan, and D. P. Frazier Emerging Roles of DMP1 in Lung Cancer Cancer Res., June 15, 2008; 68(12): 4487 - 4490. [Abstract] [Full Text] [PDF]

				J. P. O'Rourke and S. A. Ness Alternative RNA Splicing Produces Multiple Forms of c-Myb with Unique Transcriptional Activities Mol. Cell. Biol., March 15, 2008; 28(6): 2091 - 2101. [Abstract] [Full Text] [PDF]

				M. Rizzi, M. P. Tschan, C. Britschgi, A. Britschgi, B. Hugli, T. J. Grob, N. Leupin, B. U. Mueller, H.-U. Simon, A. Ziemiecki, et al. The death-associated protein kinase 2 is up-regulated during normal myeloid differentiation and enhances neutrophil maturation in myeloid leukemic cells J. Leukoc. Biol., June 1, 2007; 81(6): 1599 - 1608. [Abstract] [Full Text] [PDF]

				Z. Yang, Y. Sui, S. Xiong, S. S. Liour, A. C. Phillips, and L. Ko Switched alternative splicing of oncogene CoAA during embryonal carcinoma stem cell differentiation Nucleic Acids Res., March 4, 2007; 35(6): 1919 - 1932. [Abstract] [Full Text] [PDF]

				L. Ding, A. Sabo, N. Berkowicz, R. R. Meyer, Y. Shotland, M. R. Johnson, K. H. Pepin, R. K. Wilson, and J. Spieth EAnnot: A genome annotation tool using experimental evidence Genome Res., December 1, 2004; 14(12): 2503 - 2509. [Abstract] [Full Text] [PDF]