Elevated c-Jun expression in acute myeloid leukemias inhibits C/EBPα DNA binding via leucine zipper domain interaction

Rangatia, Janki; Vangala, Rajani Kanth; Singh, Sheo Mohan; Zada, Abdul Ali Peer; Elsässer, Annika; Kohlmann, Alexander; Haferlach, Torsten; Tenen, Daniel G.; Hiddemann, Wolfgang; Behre, Gerhard

doi:10.1038/sj.onc.1206664

Cited by 56 publications

(45 citation statements)

References 31 publications

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“…Pathway analysis revealed that many of the identified genes are dysregulated as a consequence of the activation of the transcription factors Fos, Jun, and/or Egr1 ( Figure 5A). These genes have indeed been implicated in the pathogenesis of many tumors, including AML, and are intimately connected to the control of cell proliferation and/or apoptosis [34][35][36][37][38][39] ; further, Egr1 is important for the development of the macrophage lineage. 40,41 Similarly, the dysregulation of Tnf in murine APL cells may also alter the expression of a number of other target genes.…”

Section: Discussionmentioning

confidence: 99%

Commonly dysregulated genes in murine APL cells

Yuan

Payton

Holt³

et al. 2006

Blood

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To identify genes that are commonly dysregulated in a murine model of acute promyelocytic leukemia (APL), we first defined gene expression patterns during normal murine myeloid development; serial gene expression profiling studies were performed with primary murine hematopoietic progenitors that were induced to undergo myeloid maturation in vitro with G-CSF. Many genes were reproducibly expressed in restricted developmental "windows," suggesting a structured hierarchy of expression that is relevant for the induction of developmental fates and/or differentiated cell functions. We compared the normal myeloid developmental transcriptome with that of APL cells derived from mice expressing PML-RAR␣ under control of the murine cathepsin G locus. While many promyelocytespecific genes were highly expressed in all APL samples, 116 genes were reproducibly dysregulated in many independent APL samples, including Fos, Jun, Egr1, Tnf, and Vcam1. However, this set of commonly dysregulated genes was expressed normally in preleukemic, early myeloid cells from the same mouse model, suggesting that dysregulation occurs as a "downstream" event during disease progression. These studies suggest that the genetic events that lead to APL progression may converge on common pathways that are important for leukemia pathogenesis. (Blood. 2007;109: 961-970)

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Section: Discussionmentioning

confidence: 99%

Commonly dysregulated genes in murine APL cells

Yuan

Payton

Holt³

et al. 2006

Blood

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“…c-Jun or c-Fos interacts with and prevents C/EBP bZIP DNA-binding, even if the c-Fos or c-Jun BRs are deleted, suggesting direct interaction via their LZ domains (Hsu et al, 1994). Similarly, C/EBPa binds c-Jun, but not if the LZ is deleted from either of these proteins, and c-Jun inhibits C/EBPa DNA-binding (Rangatia et al, 2002(Rangatia et al, , 2003. These studies suggest, but do not prove, direct zippering (hydrophobic surface interaction) between c-Jun or c-Fos and C/EBPa or C/EBPb.…”

Section: Pu1mentioning

confidence: 99%

Transcriptional control of granulocyte and monocyte development

2007

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“…Notably, the CCAAT-binding protein C/EBP␣ can interact with the DNA-binding domain of PU.1, displacing c-Jun and allowing granulocyte development. Although c-Jun and C/EBP␣ can also associate via their leucine zipper domains, preventing C/EBP␣ from DNA binding (46), this interaction does not appear to occur in basal bsp gene regulation because no affects were observed when C/EBP␣ was ectopically expressed alone or with c-Jun.…”

Section: Discussionmentioning

confidence: 99%