title: The BCL2A1 gene as a pre-T cell receptor-induced regulator of thymocyte survival.
abstract: The pre-T cell receptor (TCR) is expressed early during T cell development and imposes a tight selection for differentiating T cell progenitors. Pre-TCR-expressing cells are selected to survive and differentiate further, whereas pre-TCR(-) cells are "negatively" selected to die. The mechanisms of pre-TCR-mediated survival are poorly understood. Here, we describe the induction of the antiapoptotic gene BCL2A1 (A1) as a potential mechanism regulating inhibition of pre-T cell death. We characterize in detail the signaling pathway involved in A1 induction and show that A1 expression can induce pre-T cell survival by inhibiting activation of caspase-3. Moreover, we show that in vitro "knockdown" of A1 expression can compromise survival even in the presence of a functional pre-TCR. Finally, we suggest that pre-TCR-induced A1 overexpression can contribute to T cell leukemia in both mice and humans.
authors.affiliation: Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Malay
authors.initials: M
authors.lastname: Mandal
authors.forename: Christine
authors.initials: C
authors.lastname: Borowski
authors.forename: Teresa
authors.initials: T
authors.lastname: Palomero
authors.forename: Adolfo A
authors.initials: AA
authors.lastname: Ferrando
authors.forename: Philipp
authors.initials: P
authors.lastname: Oberdoerffer
authors.forename: Fanyong
authors.initials: F
authors.lastname: Meng
authors.forename: Antonio
authors.initials: A
authors.lastname: Ruiz-Vela
authors.forename: Maria
authors.initials: M
authors.lastname: Ciofani
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Zuniga-Pflucker
authors.forename: Isabella
authors.initials: I
authors.lastname: Screpanti
authors.forename: A Thomas
authors.initials: AT
authors.lastname: Look
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Korsmeyer
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
authors.forename: Harald
authors.initials: H
authors.lastname: von Boehmer
authors.forename: Iannis
authors.initials: I
authors.lastname: Aifantis
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D061945:Caspase Inhibitors; D002460:Cell Line; D002470:Cell Survival; D005786:Gene Expression Regulation; D019254:Genes, bcl-2 / Q000502:physiology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000209:etiology / Q000378:metabolism; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: C096816:BCL2-related protein A1; D061945:Caspase Inhibitors; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha; D011493:Protein Kinase C; D010738:Type C Phospholipases; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3
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