The BRG1- and hBRM-Associated Factor BAF57 Induces Apoptosis by Stimulating Expression of the Cylindromatosis Tumor Suppressor Gene

ABSTRACT Mutation of BRG1, hBRM, and their associated factors, INI1 and BAF57, in primary human tumors has suggested that inactivation of human SWI/SNF (hSWI/SNF) complexes may be involved in neoplastic transformation. BT549 is an invasive human breast carcinoma cell line that lacks expression of BAF57, a key hSWI/SNF subunit that mediates interaction with transcriptional activators and corepressors. In this study we investigated the role of BAF57 in suppressing tumorigenesis by establishing BT549 stable cell lines that expresses full-length BAF57 protein. BT549 clones expressing BAF57 demonstrated marked phenotypic changes, slow growth kinetics, and restoration of contact inhibition. Altered growth was found to be due in part to cell cycle arrest and induction of apoptosis. Furthermore, microarray analysis revealed that BAF57-mediated cell death was associated with up-regulation of proapoptotic genes including the tumor suppressor familial cylindromatosis (CYLD), which was found to be a direct target of BAF57 as determined by chromatin immunoprecipitation analysis. Increased expression of CYLD in BT549 cells induced apoptosis, while its suppression by small interfering RNA inhibited cell death in BAF57 expressing BT549 cells. These findings demonstrate the importance of BAF57 in cell growth regulation and provide a novel link between hSWI/SNF chromatin remodelers and apoptosis.

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Mechanism of folate deficiency-induced apoptosis in mouse embryonic stem cells: Cell cycle arrest/apoptosis in G1/G0 mediated by microRNA-302a and tumor suppressor gene Lats2

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2012.07.014 ◽

2012 ◽

Vol 44 (11) ◽

pp. 1750-1760 ◽

Cited By ~ 18

Author(s):

Yan Liang ◽

Yuanyuan Li ◽

Zhengli Li ◽

Zhuo Liu ◽

Zhiping Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Embryonic Stem Cells ◽

Tumor Suppressor ◽

Cell Cycle Arrest ◽

Tumor Suppressor Gene ◽

Embryonic Stem ◽

Suppressor Gene ◽

Cycle Arrest ◽

Induced Apoptosis

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Decitabine Induces Change of Biological Traits in Myelodysplastic Syndromes via FOXO1 Activation

Frontiers in Genetics ◽

10.3389/fgene.2020.603956 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zheng Zhang ◽

Yan Jia ◽

Feng Xv ◽

Lu-xi Song ◽

Lei Shi ◽

...

Keyword(s):

Tumor Suppressor ◽

Myelodysplastic Syndromes ◽

Suppressor Gene ◽

Dna Demethylation ◽

Biological Traits ◽

L Cells ◽

Cycle Arrest ◽

Inactive Form ◽

Induced Apoptosis

Decitabine (DAC) is considered to be a profound global DNA demethylation, which can induce the re-expression of silenced tumor suppressor genes. Little is known about the function of tumor suppressor gene FOXO1 in myelodysplastic syndromes (MDS). To address this issue, the study firstly investigated differentially expressed genes (DEGs) for DAC treatment in MDS cell lines, then explored the role of FOXO1 through silencing its expression before DAC treatment in MDS. The results showed that FOXO1 exists in a hyperphosphorylated, inactive form in MDS-L cells. DAC treatment both induces FOXO1 expression and reactivates the protein in its low phosphorylation level. Additionally, the results also demonstrated that this FOXO1 activation is responsible for the DAC-induced apoptosis, cell cycle arrest, antigen differentiation, and immunoregulation in MDS-L cells. We also demonstrated DAC-induced FOXO1 activation upregulates anti-tumor immune response in higher-risk MDS specimens. Collectively, these results suggest that DAC induces FOXO1 activation, which plays an important role in anti-MDS tumors.

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DMPK is a New Candidate Mediator of Tumor Suppressor p53-Dependent Cell Death

Molecules ◽

10.3390/molecules24173175 ◽

2019 ◽

Vol 24 (17) ◽

pp. 3175

Author(s):

Katsuhiko Itoh ◽

Takahiro Ebata ◽

Hiroaki Hirata ◽

Takeru Torii ◽

Wataru Sugimoto ◽

...

Keyword(s):

Dna Damage ◽

Cell Death ◽

Tumor Suppressor ◽

Dependent Manner ◽

Tumor Suppressor P53 ◽

P53 Family ◽

Gene Encoding ◽

Myotonic Dystrophy Protein Kinase ◽

Induced Apoptosis ◽

Actomyosin Contraction

Tumor suppressor p53 plays an integral role in DNA-damage induced apoptosis, a biological process that protects against tumor progression. Cell shape dramatically changes when cells undergo apoptosis, which is associated with actomyosin contraction; however, it remains entirely elusive how p53 regulates actomyosin contraction in response to DNA-damaging agents. To identify a novel p53 regulating gene encoding the modulator of myosin, we conducted DNA microarray analysis. We found that, in response to DNA-damaging agent doxorubicin, expression of myotonic dystrophy protein kinase (DMPK), which is known to upregulate actomyosin contraction, was increased in a p53-dependent manner. The promoter region of DMPK gene contained potential p53-binding sequences and its promoter activity was increased by overexpression of the p53 family protein p73, but, unexpectedly, not of p53. Furthermore, we found that doxorubicin treatment induced p73 expression, which was significantly attenuated by downregulation of p53. These data suggest that p53 induces expression of DMPK through upregulating p73 expression. Overexpression of DMPK promotes contraction of the actomyosin cortex, which leads to formation of membrane blebs, loss of cell adhesion, and concomitant caspase activation. Taken together, our results suggest the existence of p53-p73-DMPK axis which mediates DNA-damage induced actomyosin contraction at the cortex and concomitant cell death.

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Loss of the p53 tumor suppressor gene protects neurons from kainate- induced cell death

Journal of Neuroscience ◽

10.1523/jneurosci.16-04-01337.1996 ◽

1996 ◽

Vol 16 (4) ◽

pp. 1337-1345 ◽

Cited By ~ 262

Author(s):

RS Morrison ◽

HJ Wenzel ◽

Y Kinoshita ◽

CA Robbins ◽

LA Donehower ◽

...

Keyword(s):

Cell Death ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Suppressor Gene ◽

P53 Tumor Suppressor ◽

P53 Tumor Suppressor Gene

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The Cell Death Inhibitor ARC Is Induced in a Tissue-Specific Manner by Deletion of the Tumor Suppressor Gene Men1, but Not Required for Tumor Development and Growth

PLoS ONE ◽

10.1371/journal.pone.0145792 ◽

2015 ◽

Vol 10 (12) ◽

pp. e0145792 ◽

Cited By ~ 3

Author(s):

Wendy M. McKimpson ◽

Ziqiang Yuan ◽

Min Zheng ◽

Judy S. Crabtree ◽

Steven K. Libutti ◽

...

Keyword(s):

Cell Death ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Tumor Development ◽

Suppressor Gene ◽

Tissue Specific ◽

Specific Manner

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Granzyme B-induced Cell Death Involves Induction of p53 Tumor Suppressor Gene and Its Activation in Tumor Target Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m705290200 ◽

2007 ◽

Vol 282 (45) ◽

pp. 32991-32999 ◽

Cited By ~ 20

Author(s):

Franck Meslin ◽

Jerome Thiery ◽

Catherine Richon ◽

Abdelali Jalil ◽

Salem Chouaib

Keyword(s):

Cell Death ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Granzyme B ◽

Suppressor Gene ◽

Target Cells ◽

Tumor Target ◽

P53 Tumor Suppressor ◽

P53 Tumor Suppressor Gene

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Epigenetic inactivation of the CpG demethylase TET1 as a DNA methylation feedback loop in human cancers

Scientific Reports ◽

10.1038/srep26591 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 55

Author(s):

Lili Li ◽

Chen Li ◽

Haitao Mao ◽

Zhenfang Du ◽

Wai Yee Chan ◽

...

Keyword(s):

Tumor Suppressor ◽

Feedback Loop ◽

Catalytic Domain ◽

Ectopic Expression ◽

Suppressor Gene ◽

Cpg Methylation ◽

Primary Tumors ◽

Normal Tissues ◽

Tet Proteins ◽

Induced Apoptosis

Abstract Promoter CpG methylation is a fundamental regulatory process of gene expression. TET proteins are active CpG demethylases converting 5-methylcytosine to 5-hydroxymethylcytosine, with loss of 5 hmC as an epigenetic hallmark of cancers, indicating critical roles of TET proteins in epigenetic tumorigenesis. Through analysis of tumor methylomes, we discovered TET1 as a methylated target, and further confirmed its frequent downregulation/methylation in cell lines and primary tumors of multiple carcinomas and lymphomas, including nasopharyngeal, esophageal, gastric, colorectal, renal, breast and cervical carcinomas, as well as non-Hodgkin, Hodgkin and nasal natural killer/T-cell lymphomas, although all three TET family genes are ubiquitously expressed in normal tissues. Ectopic expression of TET1 catalytic domain suppressed colony formation and induced apoptosis of tumor cells of multiple tissue types, supporting its role as a broad bona fide tumor suppressor. Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9. As only infrequent mutations of TET1 have been reported, compared to TET2, epigenetic silencing therefore appears to be the dominant mechanism for TET1 inactivation in cancers, which also forms a feedback loop of CpG methylation during tumorigenesis.

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The putative tumor suppressor gene GLTSCR2 induces PTEN-modulated cell death

Cell Death and Differentiation ◽

10.1038/sj.cdd.4402204 ◽

2007 ◽

Vol 14 (11) ◽

pp. 1872-1879 ◽

Cited By ~ 50

Author(s):

J-H Yim ◽

Y-J Kim ◽

J-H Ko ◽

Y-E Cho ◽

S-M Kim ◽

...

Keyword(s):

Cell Death ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Suppressor Gene ◽

Putative Tumor Suppressor Gene ◽

Putative Tumor Suppressor

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Ceramide induces p38 MAPK and JNK activation through a mechanism involving a thioredoxin-interacting protein-mediated pathway

Blood ◽

10.1182/blood-2007-08-106336 ◽

2008 ◽

Vol 111 (8) ◽

pp. 4365-4374 ◽

Cited By ~ 121

Author(s):

Chia-Ling Chen ◽

Chiou-Feng Lin ◽

Wen-Tsan Chang ◽

Wei-Ching Huang ◽

Chiao-Fang Teng ◽

...

Keyword(s):

Tumor Suppressor ◽

Er Stress ◽

P38 Mapk ◽

De Novo ◽

Suppressor Gene ◽

Mitogen Activated Protein Kinase ◽

Interacting Protein ◽

Thioredoxin Interacting Protein ◽

Induced Apoptosis ◽

Jnk Activation

Abstract Ceramide, a tumor-suppressor lipid, is generated by sphingomyelin hydrolysis or by de novo synthesis when cells are activated by various stress stimuli as well as when cancer cells are subjected to genotoxic chemotherapy. Ceramide may modulate apoptotic signaling pathways; however, its transcription-dependent effects remain unclear. Our data showed that actinomycin D partially inhibited ceramide-induced apoptosis. Using microarray analysis, we found that ceramide up-regulated a tumor suppressor gene called thioredoxin-interacting protein (Txnip). Similarly, the chemotherapeutic agent etoposide induced Txnip expression en route to apoptosis, which was blocked by inhibitors of ceramide production. Txnip colocalized with thioredoxin and reduced its activity, which caused dissociation of thioredoxin from apoptosis signal-regulating kinase 1 (ASK1). Cells expressing ASK1 siRNA were more resistant to ceramide-induced apoptosis. Ceramide caused ASK1-regulated p38 mitogen-activated protein kinase (MAPK) and JNK activation, as well as activation of the endoplasmic reticulum (ER) stress cascade, and pharmacologic or siRNA-mediated inhibition of p38 MAPK or JNK partially reduced ceramide-induced mitochondria-mediated apoptosis. Furthermore, ceramide-induced ASK1, p38, and JNK phosphorylation and cell apoptosis were inhibited by Txnip siRNA transfection. Taken together, we show that ceramide exhibits a mechanism of transcriptional regulation involving up-regulation of Txnip expression, also induced by etoposide, which results in ASK1 activation, ER stress, and p38 and JNK phosphorylation, all leading to apoptosis.

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