Methylosome protein 50 promotes androgen- and estrogen-independent tumorigenesis

Wei, Tong; Hsia, Jiun-Yi; Chiu, Shao‐Chih; Su, Li; Juan, Chi Chang; Lee, Yuan-Chii Gladys; Chen, Jo Mei Maureen; Chou, Hsiang; Huang, Jiao Ying; Huang, Hiang Ming; Yu, Chang Tze Ricky

doi:10.1016/j.cellsig.2014.09.014

Cited by 38 publications

(35 citation statements)

References 34 publications

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“…1B shows a mixed cytoplasmic and nuclear distribution in these cultures and that expressed FLAG-MEP50 assumes a similar distribution as endogenous MEP50. This is consistent with a previous report showing that MEP50 localizes in the nucleus and cytoplasm in lung cancer cell lines (38). These data also show that vector-expressed FLAG-MEP50 colocalizes with endogenous MEP50.…”

Section: Mep50 Distribution In the Epidermis-mep50 Localizes Insupporting

confidence: 82%

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Methylosome Protein 50 and PKCδ/p38δ Protein Signaling Control Keratinocyte Proliferation via Opposing Effects on p21Cip1 Gene Expression

Saha¹,

Eckert

2015

Journal of Biological Chemistry

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Background: Keratinocytes cease proliferation during differentiation, and the mechanism that mediates these events is not well understood. Results: PRMT5/MEP50 control p21Cip1 promoter methylation to silence gene expression, and this is reversed by PKC␦/p38␦ signaling. Conclusion: PRMT5/MEP50 and PKC␦/p38␦ signaling produce opposing actions to control keratinocyte proliferation during differentiation. Significance: This study describes cross-talk between MAPK signaling and epigenetic mechanisms to control cell proliferation.

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Section: Mep50 Distribution In the Epidermis-mep50 Localizes Insupporting

confidence: 82%

“…We find that MEP50 is abundantly expressed in the foreskin epidermis and monolayer keratinocyte cultures, where it is present in both the nucleus and cytoplasm. This localization is similar to that observed in other cell types (38). We show that MEP50 knockdown leads to a substantial reduction in cell proliferation.…”

Section: Discussionsupporting

confidence: 68%

Methylosome Protein 50 and PKCδ/p38δ Protein Signaling Control Keratinocyte Proliferation via Opposing Effects on p21Cip1 Gene Expression

Saha¹,

Eckert

2015

Journal of Biological Chemistry

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“…2a, b). Therefore, we next validated AFAP1-AS1 expression in other two independent cohorts of lung cancer GEP datasets (GSE27262 [22] and GSE18842 [23]); AFAP1-AS1 was also highly expressed in these two cohorts of lung cancer patients (20.08-and 7.53-fold upregulated, respectively, Fig. 2c, d).…”

Section: Afap1-as1 Upregulation Is Associated With Poor Prognosis In mentioning

confidence: 82%

“…Five independent cohorts of primary lung cancer GEP data and their correlated clinic data, GSE31210 [20], GSE19804 [21], GSE27262 [22], GSE18842 [23], and GSE37745 [24] were downloaded from the Gene Expression Omnibus (GEO) database. GSE31210 has 226 primary lung cancer samples and 20 normal lung samples.…”

Section: Data Mining and Analysismentioning

confidence: 99%

AFAP1-AS1, a long noncoding RNA upregulated in lung cancer and promotes invasion and metastasis

et al. 2015

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Long noncoding RNAs (lncRNAs) have emerged as a major regulator of cancer. Significant fraction of lncRNAs is represented on widely used microarray platforms; however, many of which have no known function. To discover novel lung cancer-related lncRNAs, we analyzed the lncRNA expression patterns in five sets of previously published lung cancer gene expression profile data that were represented on Affymetrix HG-U133 Plus 2.0 array, and identified dysregulated lncRNAs in lung cancer. One lncRNA, actin filament associated protein 1 antisense RNA1 (AFAP1-AS1), was the most significantly upregulated in lung cancer and associated with poor prognosis. In vitro experiments demonstrated that AFAP1-AS1 knockdown significantly inhibited the cell invasive and migration capability in lung cancer cells. AFAP1-AS1 knockdown also increased the expression of its antisense protein coding gene, actin filament associated protein 1 (AFAP1), and affected the expression levels of several small GTPase family members and molecules in the actin cytokeratin signaling pathway, which suggested that AFAP1-AS1 promoted cancer cell metastasis via regulation of actin filament integrity. Our findings extend the number of noncoding RNAs functionally implicated in lung cancer progression and highlight the role of AFAP1-AS1 as potential prognostic biomarker and therapeutic target of lung cancer.

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“…PRMT5 overexpression causes the formation of tumors in nude mice [135]. MEP50 had significant parallel roles in enhancing PRMT5 methylation of PI3-kinase to promote lung cancer tumorigenesis [142]. PRMT5 overexpression also results in increased proliferation and induced anchorage-independent colony growth [13, 135].…”

Section: Introductionmentioning

confidence: 99%

The PRMT5 arginine methyltransferase: many roles in development, cancer and beyond

Stopa

Krebs

Shechter

2015

Cell. Mol. Life Sci.

404

399

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Post-translational arginine methylation is responsible for regulation of many biological processes. The protein arginine methyltransferase 5 (PRMT5, also known as Hsl7, Jbp1, Skb1, Capsuleen, or Dart5) is the major enzyme responsible for mono- and symmetric dimethylation of arginine. An expanding literature demonstrates its critical biological function in a wide range of cellular processes. Histone and other protein methylation by PRMT5 regulate genome organization, transcription, stem cells, primordial germ cells, differentiation, the cell cycle, and spliceosome assembly. Metazoan PRMT5 is found in complex with the WD-repeat protein MEP50 (also known as Wdr77, androgen receptor coactivator p44, or Valois). PRMT5 also directly associates with a range of other protein factors, including pICln, Menin, CoPR5 and RioK1 that may alter its subcellular localization and protein substrate selection. Protein substrate and PRMT5–MEP50 post-translation modifications induce crosstalk to regulate PRMT5 activity. Crystal structures of C. elegans PRMT5 and human and frog PRMT5–MEP50 complexes provide substantial insight into the mechanisms of substrate recognition and procession to dimethylation. Enzymo-logical studies of PRMT5 have uncovered compelling insights essential for future development of specific PRMT5 inhibitors. In addition, newly accumulating evidence implicates PRMT5 and MEP50 expression levels and their methyltransferase activity in cancer tumorigenesis, and, significantly, as markers of poor clinical outcome, marking them as potential oncogenes. Here, we review the substantial new literature on PRMT5 and its partners to highlight the significance of understanding this essential enzyme in health and disease.

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Methylosome protein 50 promotes androgen- and estrogen-independent tumorigenesis

Cited by 38 publications

References 34 publications

Methylosome Protein 50 and PKCδ/p38δ Protein Signaling Control Keratinocyte Proliferation via Opposing Effects on p21Cip1 Gene Expression

Methylosome Protein 50 and PKCδ/p38δ Protein Signaling Control Keratinocyte Proliferation via Opposing Effects on p21Cip1 Gene Expression

AFAP1-AS1, a long noncoding RNA upregulated in lung cancer and promotes invasion and metastasis

The PRMT5 arginine methyltransferase: many roles in development, cancer and beyond

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