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Stat5 tetramer formation is associated with leukemogenesis. Cancer Cell 2005 Jan;7(1):87-99

Date

01/18/2005

Pubmed ID

15652752

DOI

10.1016/j.ccr.2004.12.010

Scopus ID

2-s2.0-19944431828   180 Citations

Abstract

Activation of Stat5 is frequently found in leukemias. To study the mechanism and role of Stat5 activation, we introduced a constitutively activated Stat5a mutant, cS5F, into murine bone marrow (BM) cells. BM transplantation with cS5F-transfected cells caused development of multilineage leukemias in lethally irradiated wild-type or nonirradiated Rag2(-/-) mice. The leukemic cells showed strongly enhanced levels of cS5F tetramers but unchanged cS5F dimer levels in a DNA binding assay. Moreover, Stat5a mutants engineered to form only dimers, but not tetramers, failed to induce leukemias. In addition, Stat5 tetramers were found to accumulate in excess compared to dimers in various human leukemias. These data suggest that Stat5 tetramers are associated with leukemogenesis.

Author List

Moriggl R, Sexl V, Kenner L, Duntsch C, Stangl K, Gingras S, Hoffmeyer A, Bauer A, Piekorz R, Wang D, Bunting KD, Wagner EF, Sonneck K, Valent P, Ihle JN, Beug H

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Biomarkers
Bone Marrow Cells
Bone Marrow Transplantation
Cell Lineage
Cell Transformation, Neoplastic
Cells, Cultured
DNA-Binding Proteins
Female
Genetic Complementation Test
Growth Substances
Humans
Leukemia
Liver
Male
Mice
Mice, Knockout
Milk Proteins
Mutation
Nuclear Proteins
Oncogenes
Protein Structure, Quaternary
STAT5 Transcription Factor
Spleen
Trans-Activators
Transfection
Tumor Suppressor Proteins
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5