c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function

Cheng, Shinta; Davies, Kelvin P.; Yung, Eric; Beltran, R. J.; Yu, Jin Chen; Kalpana, Ganjam V.

doi:10.1038/8811

Cited by 347 publications

(296 citation statements)

References 22 publications

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“…These consist of two imperfect repeats, Rpt1 and Rpt2 and an c-terminal putative coiled coil domain (Morozov et al, 1998). Rpt1 is required for interaction with cmyc (Cheng et al, 1999). The c-terminal coiled coil domain is likely to be involved in protein-protein interactions yet to be specified.…”

Section: Resultsmentioning

confidence: 99%

INI1 mutations in meningiomas at a potential hotspot in exon 9

et al. 2001

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SummaryRhabdoid tumours have been shown to carry somatic mutations in the INI1 (SMARCB1/hSNF5) gene. A considerable fraction of these tumours exhibit allelic losses on chromosome 22. Allelic loss on 22q also is characteristic for meningiomas, however most of these alterations are considered to be associated with mutations of the NF2 gene. We examined a series of 126 meningiomas for alterations in the INI1 gene. Four identical somatic mutations in exon 9 were detected resulting in an exchange of Arg to His in position 377 of INI1. Our observations were reproduced both by using DNA from a new round of extraction and by employing overlapping primers. This mutational hotspot therefore appears to be an important target in the formation of a fraction of meningiomas. In addition, 4 novel polymorphisms of INI1 were characterized. Our data indicate that the INI1 is a second tumour suppressor gene on chromosome 22 that may be important for the genesis of meningiomas.

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Section: Resultsmentioning

confidence: 99%

INI1 mutations in meningiomas at a potential hotspot in exon 9

et al. 2001

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“…The functional relationship of MYC with BRG1 and with the SWI/SNF complex is well established. For example, MYC physically interacts with the SWI/ SNF component, SMARCB1 ( 26 ), and BRG1 is required to regulate the expression of MYC and MYC target genes ( 16 , 27 ). In tumors carrying BRG1 mutations, this regulation is abolished, thereby preventing cell differentiation and promoting cell growth ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

MAX Inactivation in Small Cell Lung Cancer Disrupts MYC–SWI/SNF Programs and Is Synthetic Lethal with BRG1

et al. 2014

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Our knowledge of small cell lung cancer (SCLC) genetics is still very limited, amplifi cation of L-MYC , N-MYC , and C-MYC being some of the well-established gene alterations. Here, we report our discovery of tumor-specifi c inactivation of the MYC-associated factor X gene, MAX , in SCLC. MAX inactivation is mutually exclusive with alterations of MYC and BRG1 , the latter coding for an ATPase of the switch/sucrose nonfermentable (SWI/SNF) complex. We demonstrate that BRG1 regulates the expression of MAX through direct recruitment to the MAX promoter, and that depletion of BRG1 strongly hinders cell growth, specifi cally in MAX-defi cient cells, heralding a synthetic lethal interaction. Furthermore, MAX requires BRG1 to activate neuroendocrine transcriptional programs and to upregulate MYC targets, such as glycolysis-related genes. Finally, inactivation of the MAX dimerization protein, MGA, was also observed in both non-small cell lung cancer and SCLC. Our results provide evidence that an aberrant SWI/SNF-MYC network is essential for lung cancer development. SIGNIFICANCE:We discovered that the MYC-associated factor X gene, MAX , is inactivated in SCLCs. Furthermore, we revealed a preferential toxicity of the inactivation of the chromatin remodeler BRG1 in MAX-defi cient lung cancer cells, which opens novel therapeutic possibilities for the treatment of patients with SCLC with MAX-defi cient tumors. Cancer Discov; 4(3);[292][293][294][295][296][297][298][299][300][301][302][303]

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“…15 Alternatively, RSF-1 overexpression may directly contribute to tumor invasiveness and metastasis. In fact, recent studies have indicated that certain proteins contributing to metastasis, such as metastasis-associated gene in NuRD complex 25 or MYC and BRCA1 in SWI/SNF complex, 26,27 can form functional complexes with chromatin remodeling factors in promoting cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of a Chromatin Remodeling Factor, RSF-1/HBXAP, Correlates with Aggressive Oral Squamous Cell Carcinoma

Fang

Huang

et al. 2011

The American Journal of Pathology

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RSF-1, also known as hepatitis B X-antigen associated protein (HBXAP), is a subunit of an ISWI chromatin remodeling complex, remodeling and spacing factor (RSF). Recent studies have provided new evidence that chromatin remodeling participates in the pathogenesis of neoplastic diseases by altering cell cycle regulation and gene expression. In this report, we studied the biological roles of RSF-1 in oral squamous cell carcinoma (OSCC), a highly invasive neoplastic disease. Based on IHC and quantitative real-time PCR, we demonstrated that RSF-1 expression could be detected in the majority of OSCC cases, and the levels were significantly higher in OSCC cells than in their normal counterparts. Moreover, expression levels of RSF-1 significantly correlated with the presence of angiolymphatic invasion, abnormal mitoses, metastasis, tumor recurrence, and advanced stage disease at presentation. Univariate and multivariate analyses showed a significant association of RSF-1 overexpression and worse overall survival in OSCC patients. RSF-1 knockdown remarkably decreased cellular proliferation and induced apoptosis in OSCC cells with high RSF-1 expression levels, but not in those without. Taken together, our results suggest that RSF-1 up-regulation is associated with several clinicopathological features of disease aggressiveness in OSCC patients, and RSF-1 plays an important role in maintaining cellular growth and survival in OSCC.

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c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function

Cited by 347 publications

References 22 publications

INI1 mutations in meningiomas at a potential hotspot in exon 9

INI1 mutations in meningiomas at a potential hotspot in exon 9

MAX Inactivation in Small Cell Lung Cancer Disrupts MYC–SWI/SNF Programs and Is Synthetic Lethal with BRG1

Overexpression of a Chromatin Remodeling Factor, RSF-1/HBXAP, Correlates with Aggressive Oral Squamous Cell Carcinoma

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