title: Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo.
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.
authors.affiliation: Department of Experimental Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Inoue
authors.forename: Markus G
authors.initials: MG
authors.lastname: Seidel
authors.forename: Wenshu
authors.initials: W
authors.lastname: Wu
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kamizono
authors.forename: Adolfo A
authors.initials: AA
authors.lastname: Ferrando
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.forename: Johann K
authors.initials: JK
authors.lastname: Hitzler
authors.forename: Tamara I
authors.initials: TI
authors.lastname: Pestina
authors.forename: Carl W
authors.initials: CW
authors.lastname: Jackson
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Tanaka
authors.forename: Miriam J
authors.initials: MJ
authors.lastname: Chong
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McKinnon
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inukai
authors.forename: Gerard C
authors.initials: GC
authors.lastname: Grosveld
authors.forename: A Thomas
authors.initials: AT
authors.lastname: Look
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D050976:Basic-Leucine Zipper Transcription Factors; D001772:Blood Cell Count; D001792:Blood Platelets / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic; D019610:Cytoprotection; D004249:DNA Damage; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic; D006410:Hematopoiesis / Q000502:physiology / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000528:radiation effects; D006454:Hemoglobins / Q000378:metabolism; D006720:Homozygote; D020287:In Situ Nick-End Labeling; D015448:Leukemia, B-Cell / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D000071250:Snail Family Transcription Factors; D013154:Spleen / Q000378:metabolism; D015996:Survival Rate; D013950:Thymus Gland / Q000528:radiation effects; D014157:Transcription Factors / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014916:Whole-Body Irradiation; D016335:Zinc Fingers / Q000502:physiology*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D017931:DNA Primers; D004268:DNA-Binding Proteins; C489626:E2a-Hlf fusion protein, mouse; D006454:Hemoglobins; D015514:Oncogene Proteins, Fusion; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53