title: Transcriptional regulation of serine/threonine protein kinase (AKT) genes by glioma-associated oncogene homolog 1.
abstract: Aberrant activation of Hedgehog signaling has been described in a growing number of cancers, including malignant lymphomas. Here, we report that canonical Hedgehog signaling modulates the transcriptional expression of AKT genes and that AKT1 is a direct transcriptional target of GLI1. We identified two putative binding sites for GLI1 in the AKT1 promoter region and confirmed their functionality using chromatin immunoprecipitation, luciferase reporter, and site-directed mutagenesis assays. Moreover, we provide evidence that GLI1 contributes to the survival of diffuse large B-cell lymphoma (DLBCL) cells and that this effect occurs in part through promotion of the transcription of AKT genes. This finding is of interest as constitutive activation of AKT has been described in DLBCL, but causative factors that explain AKT expression in this lymphoma type are not completely known. In summary, we demonstrated the existence of a novel cross-talk at the transcriptional level between Hedgehog signaling and AKT with biological significance in DLBCL.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Agarwal
authors.forename: Changju
authors.initials: C
authors.lastname: Qu
authors.forename: Kranthi
authors.initials: K
authors.lastname: Kunkalla
authors.forename: Kranthi
authors.initials: K
authors.lastname: Kunkulla
authors.forename: Yadong
authors.initials: Y
authors.lastname: Liu
authors.forename: Francisco
authors.initials: F
authors.lastname: Vega
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Cell Death; Diffuse Large B-cell Lymphoma; GLI1; Hedgehog; Lymphoma; Transcription