Role of the proto-oncogene Pokemon in cellular transformation and ARF repression

Maeda, Takahiro; Hobbs, Robin M.; Merghoub, Taha; Guernah, Ilhem; Zelent, Arthur; Cordon‐Cardo, Carlos; Teruya‐Feldstein, Julie; Pandolfi, Pier Paolo

doi:10.1038/nature03203

Cited by 299 publications

(461 citation statements)

References 48 publications

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“…For example, ZBTB7 (Pokemon) has also been identified as a potent oncogene that can promote lymphomagenesis in mice and is up-regulated in human follicular lymphoma; moreover, like CBX7, ZBTB7 is a negative regulator of ARF (21). As shown here, CBX7 is often cooverexpressed with ZBTB7 in human follicular lymphomas, raising the possibility that these proteins act together to control expression from the INK4a/ARF locus.…”

Section: Discussionmentioning

confidence: 76%

Role of the chromobox protein CBX7 in lymphomagenesis

Scott

Gil

Hernando

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Chromobox 7 (CBX7) is a chromobox family protein and a component of the Polycomb repressive complex 1 (PRC1) that extends the lifespan of cultured epithelial cells and can act independently of BMI-1 to repress the INK4a/ARF tumor suppressor locus. To determine whether CBX7 might be oncogenic, we examined its expression pattern in a range of normal human tissues and tumor samples. CBX7 was expressed at high levels in germinal center lymphocytes and germinal center-derived follicular lymphomas, where elevated expression correlated with high c-Myc expression and a more advanced tumor grade. By targeting Cbx7 expression to the lymphoid compartment in mice, we showed that Cbx7 can initiate T cell lymphomagenesis and cooperate with c-Myc to produce highly aggressive B cell lymphomas. Furthermore, Cbx7 repressed transcription from the Ink4a/Arf locus and acted epistatically to the Arf-p53 pathway during tumorigenesis. These data identify CBX7 as a chromobox protein causally linked to cancer development and may help explain the low frequency of INK4a/ ARF mutations observed in human follicular lymphoma.Ink4a-ARF ͉ oncogene ͉ Polycomb ͉ follicular lymphoma ͉ p53

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Section: Discussionmentioning

confidence: 76%

Role of the chromobox protein CBX7 in lymphomagenesis

Scott

Gil

Hernando

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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153

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“…24 ZBTB7A/FBI-1/Pokemon, one of the POK (POZ and Kruppel-like zinc finger) families, directly binds the p19Arf promoter and can repress its activity, resulting in oncogenic transformation through inhibition of p53 activity. 30 Furthermore, loss of ZBTB7A/ Pokemon in mouse embryonic fibroblasts resulted in premature senescence and unresponsiveness to oncogenic stimuli, which was caused by aberrant upregulation of ARF. 31 We showed that the level of phosphorylated-ATM was increased during premature cellular senescence induced by PATZ1 knockdown (Figure 2f) and was decreased in cells overexpressing PATZ1 (Figure 3f).…”

Section: Discussionmentioning

confidence: 99%

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) inhibits endothelial cell senescence through a p53 dependent pathway

Cho

Kim

et al. 2011

Cell Death Differ

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Vascular cell senescence, induced by the DNA damage response or inflammatory stress, contributes to age-associated vascular disease. Using complementary DNA microarray technology, we found that the level of POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is downregulated during endothelial cell (EC) senescence. PATZ1 may have an important role as a transcriptional repressor in chromatin remodeling and transcription regulation; however, the role of PATZ1 in EC senescence and vascular aging remains unidentified. Knockdown of PATZ1 in young cells accelerated premature EC senescence, which was confirmed by growth arrest, increased p53 protein level and senescence-associated b-galactosidase (SA-b-gal) activity, and repression of EC tube formation. In contrast, overexpression of PATZ1 in senescent cells reversed senescent phenotypes. Cellular senescence induced by PATZ1 knockdown in young cells was rescued by knockdown of p53, but not by knockdown of p16 INK4a . PATZ1 knockdown increased ROS levels, and pretreatment with N-acetylcysteine abolished EC senescence induced by PATZ1 knockdown. Notably, PATZ1 immunoreactivity was lower in ECs of atherosclerotic tissues than those of normal arteries in LDLR À/À mice, and immunoreactivity also decreased in ECs of old human arteries. These results suggest that PATZ1 may have an important role in the regulation of EC senescence through an ROS-mediated p53-dependent pathway and contribute to vascular diseases associated with aging.

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“…These proteins have been demonstrated to participate in a wide variety of cellular functions including transcription regulation, cellular proliferation, apoptosis, cell morphology, ion channel assembly, and protein degradation through ubiquitination (1). A subset of BTB/POZ proteins have been implicated in human cancer, and they include BCL-6 (4, 5), PLZF (promyelocytic leukemia zinc finger) (4,6), leukemia/lymphoma-related factor (LRF)/Pokemon (7,8), HIC-1 (hypermethylated in cancer-1), and Kaiso (9,10). Among them, the BCL-6 gene is the best characterized oncogene.…”

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confidence: 99%

A BTB/POZ protein, NAC-1, is related to tumor recurrence and is essential for tumor growth and survival

Nakayama¹,

Nakayama²,

Davidson

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Recent studies have suggested an oncogenic role of the BTB/POZdomain genes in hematopoietic malignancy. The aim of this study is to identify and characterize BTB/POZ-domain genes in the development of human epithelial cancers, i.e., carcinomas. In this study, we focused on ovarian carcinoma and analyzed gene expression levels using the serial analysis of gene expression (SAGE) data in all 130 deduced BTB/POZ genes. Our analysis reveals that NAC-1 is significantly overexpressed in ovarian serous carcinomas and several other types of carcinomas. Immunohistochemistry studies in ovarian serous carcinomas demonstrate that NAC-1 is localized in discrete nuclear bodies (tentatively named NAC-1 bodies), and the levels of NAC-1 expression correlate with tumor recurrence. Furthermore, intense NAC-1 immunoreactivity in primary tumors predicts early recurrence in ovarian cancer. Both coimmunoprecipitation and double immunofluorescence staining demonstrate that NAC-1 molecules homooligomerize through the BTB/POZ domain. Induced expression of the NAC-1 mutant containing only the BTB/POZ domain disrupts NAC-1 bodies, prevents tumor formation, and promotes tumor cell apoptosis in established tumors in a mouse xenograft model. Overexpression of full-length NAC-1 enhanced tumorigenicity of ovarian surface epithelial cells and NIH 3T3 cells in athymic nu/nu mice. In summary, NAC-1 is a tumor recurrence-associated gene with oncogenic potential, and the interaction between BTB/POZ domains of NAC-1 proteins is critical to form the discrete NAC-1 nuclear bodies and essential for tumor cell proliferation and survival.oncogene ͉ ovarian cancer ͉ serial analysis of gene expression

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Role of the proto-oncogene Pokemon in cellular transformation and ARF repression

Cited by 299 publications

References 48 publications

Role of the chromobox protein CBX7 in lymphomagenesis

Role of the chromobox protein CBX7 in lymphomagenesis

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) inhibits endothelial cell senescence through a p53 dependent pathway

A BTB/POZ protein, NAC-1, is related to tumor recurrence and is essential for tumor growth and survival

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