CTCF functions as a critical regulator of cell-cycle arrest and death after ligation of the B cell receptor on immature B cells

Qi, Chen‐Feng; Mårtensson, Annica; Mattioli, Michela; Dalla‐Favera, Riccardo; Lobanenkov, Victor; Morse, Herbert C.

doi:10.1073/pnas.0237127100

Cited by 65 publications

(84 citation statements)

References 37 publications

(39 reference statements)

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“…Stimulation of B cells through CD40 results in the induction of G1/S cyclin-D2 and degradation of cyclin inhibitor p27 kip-1 , which are critical for cell-cycle progression [38,44,45]. As CD40-induced proliferation is defective in CARMA1 KO B cells, we sought to determine the induction of cyclin-D2 and degradation of p27 kip-1 upon CD40 stimulation.…”

Section: Cell-cycle Progression In Cd40-stimulated Carma1 Ko B Cellsmentioning

confidence: 99%

Potential role of CARMA1 in CD40‐induced splenic B cell proliferation and marginal zone B cell maturation

Pappu¹,

Lin²

2006

Eur J Immunol

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NF‐κB activation through B cell receptor (BCR) ligation is critical for B cell development, survival and antigen‐mediated activation of B cells. CARD domain and MAGUK‐domain containing protein‐1 (CARMA1), recently identified adaptor molecule, has been shown to play an essential role in BCR‐induced NF‐κB activation. CARMA1‐deficient B cells fail to proliferate upon BCR stimulation, leading to defective humoral responses. Surprisingly, CARMA1‐deficient B cells are also defective in CD40‐induced proliferation. The mechanisms responsible for CD40‐induced proliferation defect have not yet been characterized. In this study, we show that signaling cascades activated by CD40 stimulation are largely unaffected in CARMA1‐deficient B cells. Instead, we have found that the defective proliferation of CARMA1‐deficient B cells is due to two events. First, CARMA1‐deficient B cells show defective cell‐cycle progression. Secondly, the numbers of marginal zone (MZ) B cells, which are the main responders upon CD40 stimulation, are greatly diminished in CARMA1‐deficient mice. Since B cell maturation requires basal signaling through BCR and NF‐κB activation, we propose that impaired BCR signaling in CARMA1‐deficient mice leads to defective maturation of MZ B cell population, which in turn, contributes to impaired proliferation upon CD40 stimulation.

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Section: Cell-cycle Progression In Cd40-stimulated Carma1 Ko B Cellsmentioning

confidence: 99%

Potential role of CARMA1 in CD40‐induced splenic B cell proliferation and marginal zone B cell maturation

Pappu¹,

Lin²

2006

Eur J Immunol

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“…The tumour suppressor role of CTCF in cancer is suspected because of its involvement in regulating the expression of some genes that are directly implicated in cancer (i.e., MYC, IGF2, p53, P27, p19/ARF and BRCA1) [45][46][47] and its cell growth inhibitory effect. In addition, some tumour specific mutations within the zinc finger domain have previously been detected in some tumours, including breast cancer 48,49 and a tumour-suppressor role of E2F-4 has previously been suggested in breast cancer.…”

Section: B) Two Transcription Factors: Ctcf and E2f-4mentioning

confidence: 99%

High‐resolution analysis of 16q22.1 in breast carcinoma using DNA amplifiable probes (multiplex amplifiable probe hybridization technique) and immunohistochemistry

Rakha

Armour

Pinder

et al. 2005

Intl Journal of Cancer

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Loss of the chromosomal material at 16q22.1 is one of the most frequent genetic aberrations found in both lobular and low-grade nonlobular invasive carcinoma of the breast, indicating the presence of a tumour suppressor gene (TSG) at this region in these tumours. However, the TSG (s) at the 16q22.1 in the more frequent nonlobular carcinomas is still unknown. Multiplex Amplifiable Probe Hybridisation (MAPH) is a simple, accurate and a high-resolution technique that provides an alternative approach to DNA copy-number measurement. The aim of our study was to examine the most likely candidate genes at 16q22.1 using MAPH assay combined with protein expression analysis by immunohistochemistry. We identified deletion at 16q22.1 that involves some or all of these genes. We also noticed that the smallest region of deletion at 16q22.1 could be delineated to a 3 Mb region centromeric to the P-cadherin gene. Apart from the correlation between E-cadherin protein expression and its gene copy number, no correlation was detected between the expression of E2F-4, CTCF, TRF2 or P-cadherin with their gene's copy number. In the malignant tissues, no significant loss or decrease of protein expression of any gene other than E-cadherin was seen in association with any specific tumour type. No expression of VE-cadherin or Ksp-cadherin was detected in the normal and/or malignant tissues of the breast in these cases. However, there was a correlation between increased nuclear expression of E2F-4 and tumours with higher histological grade (p ‫؍‬ 0.04) and positive lymph node disease (p ‫؍‬ 0.02), suggesting that it may have an oncogenic rather than a tumour suppressor role. The malignant breast tissues also showed abnormal cytoplasmic cellular localisation of CTCF, compared to its expression in the normal parenchymal cells. In conclusion, we have demonstrated that MAPH is a potential technique for assessment of genomic imbalances in malignant tissues. Although our results support E-cadherin as the TSG in invasive lobular carcinoma, they argue against the candidacy of E2F-4, CTCF, TRF2, P-cadherin, Ksp-cadherin and VE-cadherin as TSGs in breast cancer.

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“…However, the role of CTCF in regulating cell growth and apoptosis is still not clearly understood. In lymphocyte B cells, increased expression of CTCF is associated with downregulation of c-Myc, resulting in cell growth arrest and cell death [15]. Accumulation of CTCF in the nucleoli is related to growth arrest and apoptosis during differentiation in human K562 myeloid cells and in human breast carcinoma cells, respectively [16,17].…”

Section: Introductionmentioning

confidence: 99%

Functional role of CCCTC binding factor (CTCF) in stress-induced apoptosis

2007

Experimental Cell Research

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CTCF, a nuclear transcriptional factor, is a multifunctional protein and involves regulation of growth factor-and cytokine-induced cell proliferation/differentiation. In the present study, we investigated the role of CTCF in protecting stress-induced apoptosis in various human cell types. We found that UV irradiation and hyper-osmotic stress induced human corneal epithelial (HCE) and hematopoietic myeloid cell apoptosis detected by significantly increased caspase 3 activity and decreased cell viability. The stress-induced apoptotic response in these cells requires down-regulation of CTCF at both mRNA and protein levels, suggesting that CTCF may play an important role in downstream events of stress-induced signaling pathways. Inhibition of NFκB activity prevented stress-induced down-regulation of CTCF and increased cell viability against stress-induced apoptosis. The antiapoptotic effect of CTCF was further studied by manipulating CTCF activities in HCE and hematopoietic cells. Transient transfection of cDNAs encoding full-length human CTCF markedly suppressed stress-induced apoptosis in these cells. In contrast, knocking down of CTCF mRNA using siRNA specific to CTCF significantly promoted stress-induced apoptosis. Thus, our results reveal that CTCF is a down stream target of stress-induced signaling cascades and it plays a significant antiapoptotic role in regulation of stress-induced cellular responses in HCE and hematopoietic myeloid cells.

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CTCF functions as a critical regulator of cell-cycle arrest and death after ligation of the B cell receptor on immature B cells

Cited by 65 publications

References 37 publications

Potential role of CARMA1 in CD40‐induced splenic B cell proliferation and marginal zone B cell maturation

Potential role of CARMA1 in CD40‐induced splenic B cell proliferation and marginal zone B cell maturation

High‐resolution analysis of 16q22.1 in breast carcinoma using DNA amplifiable probes (multiplex amplifiable probe hybridization technique) and immunohistochemistry

Functional role of CCCTC binding factor (CTCF) in stress-induced apoptosis

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