PU.1 is regulated by NF-κB through a novel binding site in a 17 kb upstream enhancer element

Bonadies, Nicolas; Neururer, Ch; Steege, Andreas; Vallabhapurapu, Subrahmanya D.; Pabst, Thomas; Mueller, Beatrice U.

doi:10.1038/onc.2009.371

Cited by 39 publications

(26 citation statements)

References 39 publications

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“…35 Because CEBPA and NF-kB proteins can interact in target gene activation, suppressed levels of CEBPA protein-mediated by activation of PDI-might be involved in blocked NF-kB-dependent target gene expression. 36,37 We previously showed that the UPR is activated in a considerable subset of AML patients indicating a role of the UPR in the pathogenesis of these leukemias. 21,38 Here, we report that PDI is activated in AML patients with induced UPR.…”

Section: Discussionmentioning

confidence: 99%

Protein disulfide isomerase blocks CEBPA translation and is up-regulated during the unfolded protein response in AML

Haefliger

Klebig

Schaubitzer

et al. 2011

Blood

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Section: Discussionmentioning

confidence: 99%

Protein disulfide isomerase blocks CEBPA translation and is up-regulated during the unfolded protein response in AML

Haefliger

Klebig

Schaubitzer

et al. 2011

Blood

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“…Recently, PU.1 was reported to be the transcription factor responsible for T H 9 differentiation [175]. In unrelated recent work on acute myelogenous leukemia, it was noted that NF-κB regulates the transcription of PU.1 [176]. Furthermore, it has been suggested that IL-9 expression in T cells is regulated by NF-κB [177].…”

Section: T-cell Responses Mediated By Nf-κbmentioning

confidence: 99%

NF-κB in immunobiology

2011

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NF-κB was first discovered and characterized 25 years ago as a key regulator of inducible gene expression in the immune system. Thus, it is not surprising that the clearest biological role of NF-κB is in the development and function of the immune system. Both innate and adaptive immune responses as well as the development and maintenance of the cells and tissues that comprise the immune system are, at multiple steps, under the control of the NF-κB family of transcription factors. Although this is a well-studied area of NF-κB research, new and significant findings continue to accumulate. This review will focus on these areas of recent progress while also providing a broad overview of the roles of NF-κB in mammalian immunobiology.

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“…41 Our results add Sox4 to this list of regulatory factors controlling Sfpi1 transcription. Our ChIP studies suggest that Sox4 binds to the previously identified Tcf-binding site within the URE in myeloid cells.…”

Section: The Role Of the Ure In Regulating Sfpi1 Expression And Leukementioning

confidence: 99%

Sox4 cooperates with PU.1 haploinsufficiency in murine myeloid leukemia

Aue

Cleveland

et al. 2011

Blood

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Cooperation of multiple mutations is thought to be required for cancer development. In previous studies, murine myeloid leukemias induced by transducing wild-type bone marrow progenitors with a SRY sex determining region Y-box 4 (Sox4)-expressing retrovirus frequently carried proviral insertions at Sfpi1, decreasing its mRNA levels, suggesting that reduced Sfpi1 expression cooperates with Sox4 in myeloid leukemia induction. In support of this hypothesis, we show here that mice receiving Sox4 virus-infected Sfpi1 ko/؉ bone marrow progenitors developed myeloid leukemia with increased penetrance and shortened latency. Interestingly, Sox4 expression further decreased Sfpi1 transcription. Ectopic SOX4 expression reduced endogenous PU.1 mRNA levels in HL60 promyelocytes, and decreased Sfpi1 mRNA levels were also observed in the spleens of leukemic and preleukemic mice receiving Sox4 virus-infected wild-type bone marrow cells. In addition, Sox4 protein bound to a critical upstream regulatory element of Sfpi1 in ChIP assays. Such cooperation probably occurs in de novo human acute myeloid leukemias, as an analysis of 285 acute myeloid leukemia patient samples found a significant negative correlation between SOX4 and PU.1 expression. Our results establish a novel cooperation between Sox4 and reduced Sfpi1 expression in myeloid leukemia development and suggest that SOX4 could be an important new therapeutic target in human acute myeloid leukemia. (Blood. 2011;118(17):4674-4681) IntroductionSRY sex determining region Y-box 4 (Sox4) is a member of the SOX (SRY-related HMG-box) transcription factor family and is an important regulator of mammalian development. Homozygous deletion of Sox4 in mice results in embryonic lethality because of defective formation of the cardiac outflow tract. 1 B-and T-cell development in these Sox4-deficient embryos is also severely impaired, indicating that Sox4 function is critical for normal differentiation and expansion of the lymphoid lineages. 1,2 A role for Sox4 in cancer development was first suggested by the identification of viral insertions, activating Sox4 expression in leukemias developing in inbred strains of mice carrying endogenous retroviruses. 3 Overexpression of Sox4 was also found to block differentiation of 32Dcl.3 myeloid progenitor cells. 4 Sox4 was confirmed as an oncogene when transplantation of primary mouse bone marrow cells infected with a Sox4-expressing retroviral vector resulted in myeloid leukemia development in recipient mice. 3 The link between SOX4 and oncogenesis is not limited to leukemias, as it was also found to be overexpressed in human solid tumors, including medulloblastoma, 5 colon, 6 prostate, 7 and lung cancers. 8 However, despite overexpression of SOX4 in these tumors, a tumor-suppressive function for SOX4 has also been suggested in lung and bladder cancer cell lines, 7,9 reflecting a potential cell context-dependent role of SOX4 in tumorigenesis.There is a paucity of data about the molecular mechanisms through which SOX4 can exert an oncogenic function...

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PU.1 is regulated by NF-κB through a novel binding site in a 17 kb upstream enhancer element

Cited by 39 publications

References 39 publications

Protein disulfide isomerase blocks CEBPA translation and is up-regulated during the unfolded protein response in AML

Protein disulfide isomerase blocks CEBPA translation and is up-regulated during the unfolded protein response in AML

NF-κB in immunobiology

Sox4 cooperates with PU.1 haploinsufficiency in murine myeloid leukemia

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