title: The tumor suppressor Caliban regulates DNA damage-induced apoptosis through p53-dependent and -independent activity.
abstract: We previously identified Caliban (Clbn) as the Drosophila homolog of human Serologically defined colon cancer antigen 1 gene and demonstrated that it could function as a tumor suppressor in human non-small-cell lung cancer (NSCLC) cells, although its mode of action was unknown. Herein, we identify roles for Clbn in DNA damage response. We generate clbn knockout flies using homologous recombination and demonstrate that they have a heightened sensitivity to irradiation. We show that normal Clbn function facilitates both p53-dependent and -independent DNA damage-induced apoptosis. Clbn coordinates different apoptosis pathways, showing a two-stage upregulation following DNA damage. Clbn has proapoptotic functions, working with both caspase and the proapoptotic gene Hid. Finally, ecotopic expression of clbn(+) in NSCLC cells suppresses tumor formation in athymic nude mice. We conclude that Caliban is a regulator of DNA damage-induced apoptosis, functioning as a tumor suppressor in both p53-dependent and -independent pathways.
authors.affiliation: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: B H
authors.initials: BH
authors.lastname: Joshi
authors.forename: R K
authors.initials: RK
authors.lastname: Puri
authors.forename: B
authors.initials: B
authors.lastname: Stultz
authors.forename: Q
authors.initials: Q
authors.lastname: Yuan
authors.forename: Y
authors.initials: Y
authors.lastname: Bai
authors.forename: P
authors.initials: P
authors.lastname: Zhou
authors.forename: Z
authors.initials: Z
authors.lastname: Yuan
authors.forename: D A
authors.initials: DA
authors.lastname: Hursh
authors.forename: X
authors.initials: X
authors.lastname: Bi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C506864:Clbn protein, Drosophila; D029721:Drosophila Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins