Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Inoue, A; Seidel, MG; Wu, W; Kamizono, S; Ferrando, AA; Bronson, RT; Iwasaki, H; Akashi, K; Morimoto, A; Hitzler, JK; Pestina, TI; Jackson, CW; Tanaka, R; Chong, MJ; McKinnon, PJ; Inukai, T; Grosveld, GC; Look, AT.
Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo.
Cancer Cell. 2002; 2(4):279-288
Doi: 10.1016/S1535-6108(02)00155-1
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- Abstract:
- We show here that a zinc finger transcriptional repressor, Slug, which is aberrantly upregulated by the E2A-HLF oncoprotein in pro-B cell acute leukemia, functions as an antiapoptotic factor in normal hematopoietic progenitor cells. Slug(-/-) mice were much more radiosensitive than wild-type mice, dying earlier and showing accentuated decreases in peripheral blood cell counts, as well as abundant microhemorrhages and widely disseminated bacterial microabscesses throughout the body. Slug expression was detected in diverse subsets of hematopoietic progenitors, but not in more differentiated B and T lymphoid cells, and there was a significant increase in apoptotic (TUNEL-positive) bone marrow progenitor cells in irradiated Slug(-/-) mice compared to wild-type controls. These results implicate Slug in a novel survival pathway that protects hematopoietic progenitors from apoptosis after DNA damage.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis - radiation effects
- Basic-Leucine Zipper Transcription Factors -
- Blood Cell Count -
- Blood Platelets - metabolism
- Bone Marrow - metabolism
- Cell Lineage -
- Cell Transformation, Neoplastic -
- Cytoprotection -
- DNA Damage -
- DNA Primers - chemistry
- DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism
- Female -
- Gamma Rays -
- Gene Expression Regulation, Neoplastic -
- Hematopoiesis - physiology Hematopoiesis - radiation effects
- Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - radiation effects
- Hemoglobins - metabolism
- Homozygote -
- In Situ Nick-End Labeling -
- Leukemia, B-Cell - genetics Leukemia, B-Cell - metabolism
- Male -
- Mice -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Oncogene Proteins, Fusion - genetics Oncogene Proteins, Fusion - metabolism
- Polymerase Chain Reaction -
- Recombination, Genetic -
- Spleen - metabolism
- Survival Rate -
- Thymus Gland - radiation effects
- Transcription Factors - physiology
- Tumor Suppressor Protein p53 - metabolism
- Whole-Body Irradiation -
- Zinc Fingers - physiology