Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter

Jang, Ja Young; Choi, Young Il; Choi, Jinwook; Lee, K. Y.; Chung, Hyun Kee; Jeon, Sung Ho; Seong, Rho Hyun

doi:10.1038/sj.cdd.4401827

Cited by 22 publications

(14 citation statements)

References 44 publications

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“…The reduced GR expression may be related to elevated expression of Hes1, a transcription factor known to downregulate GR expression [21]. Also, Deltex-1 has been shown to confer GC resistance in thymocytes [22]. The ICN level is unaffected by Dex treatment (Figure 3, panel f).…”

Section: Resultsmentioning

confidence: 99%

A Role for Bcl-2 in Notch1-Dependent Transcription in Thymic Lymphoma Cells

Sionov¹,

Kfir‐Erenfeld²,

Spokoini³

et al. 2012

Advances in Hematology

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Notch1 is a transcription factor important for T-cell development. Notch1 is active in double negative (DN) thymocytes, while being depressed in double positive (DP) thymocytes. Synchronously, the expression of Bcl-2 becomes downregulated during the transition from DN to DP thymocytes. We previously observed that overexpression of an intracellular active Notch1 (ICN) in Bcl-2-positive 2B4 T cells leads to the transcription of Notch1-regulated genes. However, these genes were not induced in Bcl-2-negative DP PD1.6 thymic lymphoma cells overexpressing ICN. Here we show that, when Bcl-2 is simultaneously introduced into these cells, Notch-regulated genes are transcribed. Only in the presence of both Bcl-2 and ICN, PD1.6 thymic lymphoma cells become resistant to glucocorticoid (GC)-induced apoptosis. Our data suggest that Bcl-2 plays a role in modulating Notch1 function in T cells.

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Section: Resultsmentioning

confidence: 99%

A Role for Bcl-2 in Notch1-Dependent Transcription in Thymic Lymphoma Cells

Sionov¹,

Kfir‐Erenfeld²,

Spokoini³

et al. 2012

Advances in Hematology

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“…Recently, Weng et al [7] have found activated Notch-1 gene in the majority of samples from patients with T-ALL. Notch-1 has been shown to inhibit T-cell receptorinduced apoptosis in mature cells and dexamethasone-mediated apoptosis in thymocytes and to be antiapoptotic in T cells [8,9]. More and more evidence suggests cancers with activated Notch-1 signal are chemo-resistant [10,11].…”

Section: Introductionmentioning

confidence: 97%

Down-regulation of Notch-1 increases co-cultured Jurkat cell sensitivity to chemotherapy

Guo

et al. 2009

Leukemia & Lymphoma

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The bone marrow (BM) microenvironment plays a critical role in malignant cell growth, patient survival and response to chemotherapy in hematologic malignancies. However, the molecular mechanisms of BM stromal cells (BMSCs)-mediated survival of tumor cell remain unclear. In this study, to further evaluate the role of Notch-1 in vivo microenvironment, we investigated the influence of inhibiting Notch-1 pathway by Notch-1 siRNA on Jurkat cells in the co-culture system. We found that Notch-1 signaling in Jurkat cells was further activated by interaction with BMSCs, which inhibited drug-induced apoptosis in Jurkat cells. Notch-1 siRNA down-regulated Notch-1 and restored drug-induced apoptosis in co-cultured Jurkat cells. The possible mechanism of restoration of sensitivity to chemotherapy could be associated with repressed Akt signaling. The results indicated that Notch-1 may be a potential mechanism of BMSCs involvement in the protection of hematopoietic malignant cells from drug-induced apoptosis.

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“…Indeed, Notch has been shown to regulate apoptosis in a number of mature cell types, including thymocytes, as well as some cancers [10][11][12]. Furthermore, Notch pathway components are re-expressed in exocrine cells after experimentally induced pancreas injury [13,14].…”

Section: Introductionmentioning

confidence: 99%