Evidence that the Pim1 kinase gene is a direct target of HOXA9.

Evidence that the Pim1 kinase gene is a direct target of HOXA9. Research Abstract Details 

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Evidence that the Pim1 kinase gene is a direct target of HOXA9. Abstract Text:

Yu-Long Hu,Emmanuelle ,Stephen Fong,Corey Largman,Hugh Jeffrey Lawrence,

The HOXA9 homeoprotein exerts dramatic effects in hematopoiesis. Enforced expression of HOXA9 enhances proliferation of primitive blood cells, expands hematopoietic stem cells (HSCs), and leads to myeloid leukemia. Conversely, loss of HOXA9 inhibits proliferation and impairs HSC function. The pathways by which HOXA9 acts are largely unknown, and although HOXA9 is a transcription factor, few direct target genes have been identified. Our previous study suggested that HOXA9 positively regulates Pim1, an oncogenic kinase. The hematologic phenotypes of Hoxa9- and Pim1-deficient animals are strikingly similar. Here we show that HOXA9 protein binds to the Pim1 promoter and induces Pim1 mRNA and protein in hematopoietic cells. Pim1 protein is diminished in Hoxa9(-/-) cells, and Hoxa9 and Pim1 mRNA levels track together in early hematopoietic compartments. Induction of Pim1 protein by HOXA9 increases the phosphorylation and inactivation of the proapoptotic BAD protein, a target of Pim1. Hoxa9(-/-) cells show increased apoptosis and decreased proliferation, defects that are ameliorated by reintroduction of Pim1. Thus Pim1 appears to be a direct transcriptional target of HOXA9 and a mediator of its antiapoptotic and proproliferative effects in early cells. Since HOXA9 is frequently up-regulated in acute myeloid leukemia, Pim1 may be a therapeutic target in human disease.

Evidence that the Pim1 kinase gene is a direct target of HOXA9. Publishing Authors By Initials

YL Hu,E ,S Fong,C Largman,HJ Lawrence,

For similar cells: cells, cultured: cell line: cell line, tumor: u937 cells research abstracts see: cells: cells, cultured: cell line: cell line, tumor: u937 cells research

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Evidence that the Pim1 kinase gene is a direct target of HOXA9. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Blood

VOLUME: 109

Page Numbers: 4732-8

Journal Abbreviation: Blood

ISSN: 0006-4971

DAY: 27

MONTH: 02

YEAR: 2007

Evidence that the Pim1 kinase gene is a direct target of HOXA9. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7603509

Evidence that the Pim1 kinase gene is a direct target of HOXA9. Keywords Mesh Terms:

KEYWORDS: U937 Cells

MESH TERMS: genetics

Chemical & Substance for Abstract: Evidence that the Pim1 kinase gene is a direct target of HOXA9. Information

Substance Name: Proto-Oncogene Proteins c-pim-1

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Evidence that the Pim1 kinase gene is a direct target of HOXA9.

AFFILIATION: Hematology Research, Medical Service, UCSF Veterans Affairs Medical Center, University of California-San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: DK 48642

ACRONYM: DK

MEDLINETA: Blood

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