Critical Role of STAT5 Transcription Factor Tetramerization for Cytokine Responses and Normal Immune Function

Abstract The transcription factor T-bet is a key regulator of type 1 immune responses. We examined the role of T-bet in an animal model of immune-mediated bone marrow (BM) failure using mice carrying a germline T-bet gene deletion (T-bet−/−). In comparison with normal C57BL6 (B6) control mice, T-bet−/− mice had normal cellular composition in lymphohematopoietic tissues, but T-bet−/− lymphocytes were functionally defective. Infusion of 5 × 106 T-bet−/− lymph node (LN) cells into sublethally irradiated, major histocompatibility complex–mismatched CByB6F1 (F1) recipients failed to induce the severe marrow hypoplasia and fatal pancytopenia that is produced by injection of similar numbers of B6 LN cells. Increasing T-bet−/− LN-cell dose to 10 to 23 × 106 per recipient led to only mild hematopoietic deficiency. Recipients of T-bet−/− LN cells had no expansion in T cells or interferon-γ–producing T cells but showed a significant increase in Lin−Sca1+CD117+CD34− BM cells. Plasma transforming growth factor-β and interleukin-17 concentrations were increased in T-bet−/− LN-cell recipients, possibly a compensatory up-regulation of the Th17 immune response. Continuous infusion of interferon-γ resulted in hematopoietic suppression but did not cause T-bet−/− LN-cell expansion or BM destruction. Our data provided fresh evidence demonstrating a critical role of T-bet in immune-mediated BM failure.

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Critical role of the fibroblast growth factor signalling pathway in Ewing's sarcoma octamer‐binding transcription factor 4‐mediated cell proliferation and tumorigenesis

FEBS Journal ◽

10.1111/febs.14946 ◽

2019 ◽

Vol 286 (22) ◽

pp. 4443-4472 ◽

Cited By ~ 1

Author(s):

Junghoon Kim ◽

Hyo Sun Kim ◽

Jung‐Jae Shim ◽

Jungwoon Lee ◽

Ah‐young Kim ◽

...

Keyword(s):

Cell Proliferation ◽

Transcription Factor ◽

Growth Factor ◽

Critical Role ◽

Fibroblast Growth ◽

Growth Factor Signalling ◽

Octamer Binding Transcription Factor ◽

Transcription Factor 4 ◽

Growth Factor Signalling Pathway

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Critical Role of Activating Transcription Factor 4 in the Anabolic Actions of Parathyroid Hormone in Bone

PLoS ONE ◽

10.1371/journal.pone.0007583 ◽

2009 ◽

Vol 4 (10) ◽

pp. e7583 ◽

Cited By ~ 45

Author(s):

Shibing Yu ◽

Renny T. Franceschi ◽

Min Luo ◽

Jie Fan ◽

Di Jiang ◽

...

Keyword(s):

Transcription Factor ◽

Parathyroid Hormone ◽

Critical Role ◽

Activating Transcription Factor 4 ◽

Activating Transcription Factor ◽

Transcription Factor 4

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Down Regulation of SIRT2 Reduced ASS Induced NSCLC Apoptosis Through the Release of Autophagy Components via Exosomes

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.601953 ◽

2020 ◽

Vol 8 ◽

Author(s):

Lei Wang ◽

Pei Xu ◽

Xiao Xie ◽

Fengqing Hu ◽

Lianyong Jiang ◽

...

Keyword(s):

Transcription Factor ◽

Cell Apoptosis ◽

Critical Role ◽

Nsclc Cell ◽

Dependent Manner ◽

Cell Metastasis ◽

Rna Immunoprecipitation ◽

Transcription Factor Eb

Metastasis of cancer is the main cause of death in many types of cancer. Acute shear stress (ASS) is an important part of tumor micro-environment, it plays a crucial role in tumor invasion and spread. However, less is known about the role of ASS in tumorigenesis and metastasis of NSCLC. In this study, NSCLC cells were exposed to ASS (10 dyn/cm2) to explore the effect of ASS in regulation of autophagy and exosome mediated cell survival. Finally, the influence of SIRT2 on NSCLC cell metastasis was verified in vivo. Our data demonstrates that ASS promotes exosome and autophagy components releasing in a time dependent manner, inhibition of exosome release exacerbates ASS induced NSCLC cell apoptosis. Furthermore, we identified that this function was regulated by sirtuin 2 (SIRT2). And, RNA immunoprecipitation (RIP) assay suggested SIRT2 directly bound to the 3′UTR of transcription factor EB (TFEB) and facilitated its mRNA stability. TFEB is a key transcription factor involved in the regulation of many lysosome related genes and plays a critical role in the fusion of autophagosome and lysosome. Altogether, this data revealed that SIRT2 is a mechanical sensitive protein, and it regulates ASS induced cell apoptosis by modulating the release of exosomes and autophagy components, which provides a promising strategy for the treatment of NSCLCs.

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Deficiency of transcription factor RelB perturbs myeloid and DC development by hematopoietic-extrinsic mechanisms

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1619863114 ◽

2017 ◽

Vol 114 (15) ◽

pp. 3957-3962 ◽

Cited By ~ 16

Author(s):

Carlos G. Briseño ◽

Marco Gargaro ◽

Vivek Durai ◽

Jesse T. Davidson ◽

Derek J. Theisen ◽

...

Keyword(s):

Transcription Factor ◽

Critical Role ◽

Radiation Chimeras ◽

Severe Reduction ◽

Myeloid Development ◽

Noncanonical Pathway ◽

Β Receptor ◽

The Impact ◽

Receptor Family

RelB is an NF-κB family transcription factor activated in the noncanonical pathway downstream of NF-κB–inducing kinase (NIK) and TNF receptor family members including lymphotoxin-β receptor (LTβR) and CD40. Early analysis suggested that RelB is required for classical dendritic cell (cDC) development based on a severe reduction of cDCs in Relb−/− mice associated with profound myeloid expansion and perturbations in B and T cells. Subsequent analysis of radiation chimeras generated from wild-type and Relb−/− bone marrow showed that RelB exerts cell-extrinsic actions on some lineages, but it has remained unclear whether the impact of RelB on cDC development is cell-intrinsic or -extrinsic. Here, we reevaluated the role of RelB in cDC and myeloid development using a series of radiation chimeras. We found that there was no cell-intrinsic requirement for RelB for development of most cDC subsets, except for the Notch2- and LTβR-dependent subset of splenic CD4+ cDC2s. These results identify a relatively restricted role of RelB in DC development. Moreover, the myeloid expansion in Relb−/− mice resulted from hematopoietic-extrinsic actions of RelB. This result suggests that there is an unrecognized but critical role for RelB within the nonhematopoietic niche that controls normal myelopoiesis.

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