Transcriptional regulation of serine/threonine protein kinase (AKT) genes by glioma-associated oncogene homolog

Nitin K. Agarwal, Changju Qu, Kranthi Kunkulla, Yadong Liu, Francisco Vega

Research output: Contribution to journalArticle

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)15390-15401
Number of pages12
JournalJournal of Biological Chemistry
Volume288
Issue number21
DOIs
StatePublished - May 24 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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