Prohibitin is required for transcriptional repression by the WT1–BASP1 complex

Toska, Eneda; Shandilya, Jayasha; Goodfellow, Sarah J.; Medler, Kathryn F.; Roberts, Stefan G. E.

doi:10.1038/onc.2013.447

Cited by 34 publications

(57 citation statements)

References 48 publications

(79 reference statements)

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“…A plasmid transfection assay showed that over‐expression of BASP1 blocked the increases of WT1, and an siRNA interference assay found that reducing BASP1 up‐regulated the levels of WT1. These results are consistent with others . Based on these results, we conclude that miR‐191 targets BASP1 to up‐regulate the expression of WT1, which is implicated in malignancy‐related processes.…”

Section: Discussionsupporting

confidence: 92%

MicroRNA‐191, by promoting the EMT and increasing CSC‐like properties, is involved in neoplastic and metastatic properties of transformed human bronchial epithelial cells

et al. 2014

Molecular Carcinogenesis

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Lung cancer is the leading cause of cancer mortality worldwide. A common interest in lung cancer research is the identification of biomarkers for early diagnosis and accurate prognosis. There is increasing evidence that microRNAs (miRNAs) are involved in lung cancer. To explore new biomarkers of chemical exposure in risk assessment of chemical carcinogenesis and lung cancer, we analyzed miRNA expression profiles of human bronchial epithelial (HBE) cells malignantly transformed by arsenite. High-throughput microarray analysis showed that 51 miRNAs were differentially expressed in transformed HBE cells relative to normal HBE cells. In particular, miR-191 was up-regulated in transformed cells. In HBE cells, arsenite induced increases of miR-191 and WT1 levels, decreased BASP1 expression, and activated the Wnt/β-catenin pathway, effects that were blocked by miR-191 knockdown. In addition, a luciferase reporter assay indicated that BASP1 is a direct target of miR-191. By inhibiting the expression of BASP1, miR-191 increased the expression of WT1 to promote activation of Wnt/β-catenin pathway. In transformed cells, inhibition of miR-191 expression blocked the epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties of cells and decreased their migratory capacity and neoplastic properties. Thus, these results demonstrate that miR-191 modulates the EMT and the CSC-like properties of transformed cells and indicate that it is an onco-miR involved in the neoplastic and metastatic properties of transformed cells.

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Section: Discussionsupporting

confidence: 92%

MicroRNA‐191, by promoting the EMT and increasing CSC‐like properties, is involved in neoplastic and metastatic properties of transformed human bronchial epithelial cells

et al. 2014

Molecular Carcinogenesis

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“…In multiple carcinoma, melanoma, and leukemia cells, BASP1 transcription is silenced by promoter methylation (Kaehler et al , ; Moribe et al , ; Zhou et al , ), a typical DNA modification in the regulatory regions of tumor suppressors in cancer. An important function of BASP1 is to act as a transcriptional cosuppressor of the Wilms’ tumor suppressor protein WT1, converting the WT1 oncoprotein into a tumor suppressor (Carpenter et al , ; Goodfellow et al , ; Toska et al , ; Toska et al , ). WT1 is a gene regulator important for cell growth, apoptosis, and differentiation, and multiple genes are regulated by WT1.…”

Section: Discussionmentioning

confidence: 99%

“…Phosphorylation by PKC leads to disruption of the interactions of BASP1 with membrane lipids or CaM (Maekawa et al , ; Takasaki et al , ). BASP1 can then be translocated into the nucleus where it attenuates the transcriptional activity of the Wilms’ tumor suppressor protein WT1, thereby acting as a transcriptional cosuppressor, which also drives cell differentiation processes (Carpenter et al , ; Gao et al , ; Goodfellow et al , ; Toska et al , ; Toska et al , ).…”

Section: Introductionmentioning

confidence: 99%

The brain acid‐soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin

et al. 2020

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The MYC protein is a transcription factor with oncogenic potential controlling fundamental cellular processes such as cell proliferation, metabolism, differentiation, and apoptosis. The MYC gene is a major cancer driver, and elevated MYC protein levels are a hallmark of most human cancers. We have previously shown that the brain acid‐soluble protein 1 gene (BASP1) is specifically downregulated by the v‐myc oncogene and that ectopic BASP1 expression inhibits v‐myc‐induced cell transformation. The 11‐amino acid effector domain of the BASP1 protein interacts with the calcium sensor calmodulin (CaM) and is mainly responsible for this inhibitory function. We also reported recently that CaM interacts with all MYC variant proteins and that ectopic CaM increases the transactivation and transformation potential of the v‐Myc protein. Here, we show that the presence of excess BASP1 or of a synthetic BASP1 effector domain peptide leads to displacement of v‐Myc from CaM. The protein stability of v‐Myc is decreased in cells co‐expressing v‐Myc and BASP1, which may account for the inhibition of v‐Myc. Furthermore, suppression of v‐Myc‐triggered transcriptional activation and cell transformation is compensated by ectopic CaM, suggesting that BASP1‐mediated withdrawal of CaM from v‐Myc is a crucial event in the inhibition. In view of the tumor‐suppressive role of BASP1 which was recently also reported for human cancer, small compounds or peptides based on the BASP1 effector domain could be used in drug development strategies aimed at tumors with high MYC expression.

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“…BASP1 associates with WT1 at the promoters of WT1target genes and represses their transcription. 48,49 Different subcellular localization pattern and relative abundance of WT1 cofactors determine the binding partner preference. Although WT1 and BASP1 predominantly interact at the gene promoters and regulate transcriptional output, it is also possible that BASP1 influences WT1-mediated mitotic checkpoint function and affects the fidelity of chromosome segregation during cell cycle.…”

Section: Role Of Wt1-interacting Partners In Mitotic Checkpoint Regulmentioning

confidence: 99%

A role of WT1 in cell division and genomic stability

Shandilya

Roberts

2015

Cell Cycle

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Wilms' tumor-1 protein (WT1) is a transcription factor that can either activate or repress genes to regulate cell growth, apoptosis and differentiation. WT1 can act as either a tumor suppressor or an oncogene. The cellular functions of WT1 are predominantly regulated by its various interacting partners. Recently we have found that WT1 can regulate the fidelity of chromosome segregation through its interaction with the spindle assembly checkpoint protein, Mitotic arrest deficient-2 (MAD2). WT1 delays anaphase entry by inhibiting the ubiquitination activity of the Anaphase promoting complex/cyclosome (APC/C). Our findings have revealed an important role of WT1 in the regulation of mitotic checkpoint and genomic stability.

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Prohibitin is required for transcriptional repression by the WT1–BASP1 complex

Cited by 34 publications

References 48 publications

MicroRNA‐191, by promoting the EMT and increasing CSC‐like properties, is involved in neoplastic and metastatic properties of transformed human bronchial epithelial cells

MicroRNA‐191, by promoting the EMT and increasing CSC‐like properties, is involved in neoplastic and metastatic properties of transformed human bronchial epithelial cells

The brain acid‐soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin

A role of WT1 in cell division and genomic stability

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