Falkor, a novel cell growth regulator isolated by a functional genetic screen.
A novel cell growth regulator, named Falkor, was identified using a functional approach to mammalian gene cloning, the Genetic Supressor Elements (GSE) method. In this screen, expression of the C-terminal domain of Falkor conferred cells with resistance to cisplatin-induced growth arrest. Expression of the C-terminus of Falkor, but not of the full-length protein, enhanced cell growth both following genotoxic stress and under normal conditions suggesting a general role for this protein in cell growth control. This effect of the C-terminus fragment was abrogated by over-expression of the full-length Falkor, suggesting that the fragment counteracts the function of the full-length protein. Falkor is encoded by a 2-kb mRNA which is present at different levels in various tissues, and is localized in the nucleus of cells. The C-terminal domain of Falkor, isolated from the GSE library, has significant homology to a known human and rat cell growth regulator, SM-20, and to the C. elegans protein EGL-9, recently shown to modify the Hypoxia Inducible Factor-1alpha. The homology suggests that these proteins share a functional domain that is conserved among a family of growth regulation proteins.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D003001:Cloning, Molecular; D004249:DNA Damage; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D015723:Gene Library; D006133:Growth Substances / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D017874:Immediate-Early Proteins / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D011393:Procollagen-Proline Dioxygenase; D017385:Sequence Homology; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D004268:DNA-Binding Proteins; D006133:Growth Substances; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; C490189:Egln1 protein, mouse; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D002945:Cisplatin