Regulation of c-myc Transcription by Interleukin-2 (IL-2)

Grigorieva, I. V.; Grigoriev, Vitalii G.; Rowney, M.; Hoover, R G

doi:10.1074/jbc.275.10.7343

Cited by 17 publications

(4 citation statements)

References 57 publications

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“…Together with the fact that binding of endogenous c‐Myc to the distal promoter element is significantly enhanced upon IL‐15 stimulation in peripheral blood NK cells and correlates with an increase in KIR transcription, this provides a direct link between NK cell activation signals and KIR expression required for acquisition of the effector function during NK cell education . In addition, it has been demonstrated that stimulation with IL‐2, an important regulator of NK cell activity, increases c‐myc expression in natural killer cell line NK3.3 . However, c‐myc expression in NK cells in cancer patients has never been evaluated.…”

Section: Introductionmentioning

confidence: 99%

Alterations of oncogenes expression in NK cells in patients with cancer

Zakiryanova

Kustova²,

Urazalieva³

et al. 2017

Immunity Inflam & Disease

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IntroductionC‐kit/SCF signaling plays a key role in regulating NK cell homeostasis, maturation, proliferation, and cytotoxicity. C‐kit‐deficiency in NK cells results in significant reduction of their number, suggesting an imperative role for c‐kit signaling in NK cell biology. We have recently showed that human NK cells express not only c‐kit‐receptor, but also both membrane‐bound and soluble forms of c‐kit ligand—Stem cell factor. The goal of this study was to characterize the c‐kit/SCF autocrine loop in peripheral blood NK cells obtained from patients with cancer.MethodsUsing Smart Flare and qRT‐PCR, we have characterized expression of c‐kit and two forms of SCF in patients’ NK cells and correlated these results with the expression of c‐myc and STAT3.ResultsOur results demonstrated that the expression of proto‐oncogenes c‐myc and c‐kit was significantly decreased in NK cells from all cancer patients. Expression of membrane‐bound SCF in NK cells correlated with the presence of remote metastases.ConclusionsWe suggest that the abnormal signaling and expression of c‐kit/SCF, c‐myc, and STAT3 in NK cells is responsible for the defect in their cytolytic activity in cancer and these defects at the gene expression level may be the cause rather than the result of tumor progression.

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Section: Introductionmentioning

confidence: 99%

Alterations of oncogenes expression in NK cells in patients with cancer

Zakiryanova

Kustova²,

Urazalieva³

et al. 2017

Immunity Inflam & Disease

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“…These observations raise the possibility that regulation of c - Myc expression by STAT5 might be likewise unconventional, possibly involving distal elements. In support of this proposition, we previously attempted and failed to detect STAT5 binding along the c - Myc gene [ 13 ], including at GAS elements present in its promoter and known to mediate transcriptional response to other STAT family members [ 39 – 41 ].…”

Section: Introductionmentioning

confidence: 99%

Signal transducer and activator of transcription STAT5 is recruited to c-Myc super-enhancer

2016

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Backgroundc-Myc has been proposed as a putative target gene of signal transducer and activator of transcription 5 (STAT5). No functional STAT5 binding site has been identified so far within the c-Myc gene locus, therefore a direct transcriptional regulation by STAT5 remains uncertain. c-Myc super-enhancer, located 1.7 Mb downstream of the c-Myc gene locus, was recently reported as essential for the regulation of c-Myc gene expression by hematopoietic transcription factors and bromodomain and extra-terminal (BET) proteins and for leukemia maintenance. c-Myc super-enhancer is composed of five regulatory regions (E1–E5) which recruit transcription and chromatin-associated factors, mediating chromatin looping and interaction with the c-Myc promoter.ResultsWe now show that STAT5 strongly binds to c-Myc super-enhancer regions E3 and E4, both in normal and transformed Ba/F3 cells. We also found that the BET protein bromodomain-containing protein 2 (BRD2), a co-factor of STAT5, co-localizes with STAT5 at E3/E4 in Ba/F3 cells transformed by the constitutively active STAT5-1*6 mutant, but not in non-transformed Ba/F3 cells. BRD2 binding at E3/E4 coincides with c-Myc transcriptional activation and is lost upon treatment with deacetylase and BET inhibitors, both of which inhibit STAT5 transcriptional activity and c-Myc gene expression.ConclusionsOur data suggest that constitutive STAT5 binding to c-Myc super-enhancer might contribute to BRD2 maintenance and thus allow sustained expression of c-Myc in Ba/F3 cells transformed by STAT5-1*6.Electronic supplementary materialThe online version of this article (doi:10.1186/s12867-016-0063-y) contains supplementary material, which is available to authorized users.

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“…c-Myc plays a role in hematopoietic homeostasis, and its upregulation is essential for initiating the differentiation of HSPCs [53]. Expression of c-Myc can be upregulated by IL-2 [54]. Both c-Myc and RSK1-p90 are downstream targets of ERK1/2 [55,56].…”

Section: Discussionmentioning

confidence: 99%

The Involvement of Macrophage Colony Stimulating Factor on Protein Hydrolysate Injection Mediated Hematopoietic Function Improvement

Wang

Zhang

Meng

et al. 2021

Cells

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Protein hydrolysate injection (PH) is a sterile solution of hydrolyzed protein and sorbitol that contains 17 amino acids and has a molecular mass of 185.0–622.0 g/mol. This study investigated the effect of PH on hematopoietic function in K562 cells and mice with cyclophosphamide (CTX)-induced hematopoietic dysfunction. In these myelosuppressed mice, PH increased the number of hematopoietic cells in the bone marrow (BM) and regulated the concentration of several factors related to hematopoietic function. PH restored peripheral blood cell concentrations and increased the numbers of hematopoietic stem cells and progenitor cells (HSPCs), B lymphocytes, macrophages, and granulocytes in the BM of CTX-treated mice. Moreover, PH regulated the concentrations of macrophage colony stimulating factor (M-CSF), interleukin (IL)-2, and other hematopoiesis-related cytokines in the serum, spleen, femoral condyle, and sternum. In K562 cells, the PH-induced upregulation of hematopoiesis-related proteins was inhibited by transfection with M-CSF siRNA. Therefore, PH might benefit the BM hematopoietic system via the regulation of M-CSF expression, suggesting a potential role for PH in the treatment of hematopoietic dysfunction caused by cancer therapy.

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Regulation of c-myc Transcription by Interleukin-2 (IL-2)

Cited by 17 publications

References 57 publications

Alterations of oncogenes expression in NK cells in patients with cancer

Alterations of oncogenes expression in NK cells in patients with cancer

Signal transducer and activator of transcription STAT5 is recruited to c-Myc super-enhancer

The Involvement of Macrophage Colony Stimulating Factor on Protein Hydrolysate Injection Mediated Hematopoietic Function Improvement

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