Stra13 is induced by genotoxic stress and regulates ionizing-radiation-induced apoptosis.
In response to a number of genotoxic stimuli that induce DNA damage in cells, the tumour suppressor p53 is activated resulting in cell cycle arrest or apoptosis. In this study, we have identified stimulated with retinoic acid 13 (Stra13), a basic helix-loop-helix transcription factor, as a regulator of ionizing-radiation-induced apoptosis. We show that Stra13 is induced in response to several DNA-damaging agents in a p53-independent manner. Stra13-/- thymocytes show impaired apoptosis in response to ionizing radiation, and consistently, p53 levels and also expression of its key transcriptional targets Puma and Noxa are reduced in the mutant thymocytes. In vitro, Stra13 regulates p53 levels in a mouse double mutant 2 (Mdm2)-dependent manner by physically interacting with p53 and preventing Mdm2-mediated ubiquitination and nuclear export. Together, our studies provide evidence that Stra13 is involved in DNA-damage-induced apoptosis and indicate its role in tumorigenesis.
Thin
Tin Htwe
TH
Department of Molecular, Cell, and Developmental Biology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, New York 10029, USA.
Li
Li
L
Chung
Teng-Kai
TK
Sun
Hong
H
Taneja
Reshma
R
D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D014212:Tretinoin / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051736:Proto-Oncogene Proteins c-mdm2; D014212:Tretinoin; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C491539:Bhlhe40 protein, mouse; C488588:PUMA protein, mouse; C408009:Pmaip1 protein, mouse; C497207:Mdm2 protein, mouse