Constitutive overexpression of the integral membrane protein Itm2A enhances myogenic differentiation of C2C12 cells

plas, D. Van den; Merregaert, J.

doi:10.1016/j.cellbi.2003.11.019

Cited by 27 publications

(26 citation statements)

References 12 publications

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“…Immunohistochemical analysis of the CBFb-MYH11 protein revealed a unique nuclear localization in our M4Eo cases. 19 ITM2A, a novel type II integral membrane protein gene that is involved in T-cell development and Comparative analysis of genes in acute myeloid leukemia M4Eo X Sun et al activation, 20 myogenesis, 21 and chondrogenesis 22 was a good marker of M4Eo in this study. The expression levels of ITM2A were higher in all 18 M4Eo cases in the cDNA microarray ( þ 3.41-fold; Table 2a).…”

Section: M4eo Has a Distinct Gene Expression Profilementioning

confidence: 93%

Comparative analysis of genes regulated in acute myelomonocytic leukemia with and without inv(16)(p13q22) using microarray techniques, real-time PCR, immunohistochemistry, and flow cytometry immunophenotyping

et al. 2007

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Acute myeloid leukemia with inv(16)(p13q22), also known as M4Eo, is a distinct type of leukemia with characteristic clinicopathologic and cytogenetic features. Patients with M4Eo have monocytosis, high blast counts, and abnormal bone marrow eosinophils that contain large basophilic granules. The inv(16)(p13q22) or, less commonly, the t(16;16)(p13;q22) causes fusion of the CBFb gene at 16q22 and the MYH11 gene at 16p13, creating the novel chimeric protein CBFb-MYH11. To understand the underlying molecular mechanisms unique to M4Eo biology, we determined the gene expression profile of M4Eo cases by using cDNA and long oligonucleotide microarrays. Cases of acute myelomonocytic leukemia without CBFb-MYH11 (M4) acted as our control. We found that in the gene expression profile of M4Eo, NF-jB activators and inhibitors were upregulated and downregulated, respectively, suggesting that the NF-jB signaling pathway is activated at a higher level in M4Eo than in acute myelomonocytic leukemia M4. In addition, the gene expression profile of M4Eo indicates high cell proliferation and low apoptosis. We used real-time PCR, immunohistochemistry, and flow cytometry immunophenotyping to confirm some of our microarray data. These findings most likely represent the functional consequences of the abnormal chimeric protein CBFb-MYH11, which is unique to this disease, and suggest that NF-jB is a potential therapeutic target for treating M4Eo patients.

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Section: M4eo Has a Distinct Gene Expression Profilementioning

confidence: 93%

Comparative analysis of genes regulated in acute myelomonocytic leukemia with and without inv(16)(p13q22) using microarray techniques, real-time PCR, immunohistochemistry, and flow cytometry immunophenotyping

et al. 2007

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“…Although the roles and association of these genes with AS have not yet been reported, ITM2A is involved in osteoand chondrogenic cellular differentiation (cells responsible for the development of bone and cartilage, respectively) (Deleersnijder et al, 1996). ITM2A is also involved in the activation of T cells in the immune system (Kirchner and Bevan, 1999) and in myocyte differentiation (Van den Plas and Merregaert, 2004). Furthermore, some of the upregulated genes, e.g., ITM2A and collagen, type IX, alpha 2 (COL9A2), might modulate cartilage and bone metabolism leading to AS progression.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of differentially expressed genes in ankylosing spondylitis

Lee

Song

2015

Genet. Mol. Res.

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ABSTRACT. The purpose of this study was to identify differentially expressed (DE) genes and biological processes associated with changes in gene expression in ankylosing spondylitis (AS). We performed a metaanalysis using the integrative meta-analysis of expression data program on publicly available microarray AS Gene Expression Omnibus (GEO) datasets. We performed Gene Ontology (GO) enrichment analyses and pathway analysis using the Kyoto Encyclopedia of Genes and Genomes. Four GEO datasets, including 31 patients with AS and 39 controls, were available for the meta-analysis. We identified 65 genes across the studies that were consistently DE in patients with AS vs controls (23 upregulated and 42 downregulated). The upregulated gene with the largest effect size (ES; -1.2628, P = 0.020951) was integral membrane protein 2A (ITM2A), which is expressed by CD4+ T cells and plays a role in activation of T cells. The downregulated gene with the largest ES (1.2299, P = 0.040075) was mitochondrial ribosomal protein S11 (MRPS11). The most significant GO enrichment was in the respiratory electron transport chain category (P = 1.67 x 10 -9). Therefore, our metaanalysis identified genes that were consistently DE as well as biological pathways associated with gene expression changes in AS.

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“…16 While ITM2A expression enhances myogenic differentiation of C2C12 cells, forced ITM2A expression inhibits chondrogenic differentiation of mesenchymal stem cells. 17,18 In addition, a recent report showed that ITM2A expression is regulated by the transcription factor GATA3, which is expressed exclusively in the T cell lineage. ITM2A overexpression in mouse T cells partially suppresses CD8 expression suggesting ITM2A is involved in T cell development.…”

Section: Introductionmentioning

confidence: 99%

The integral membrane protein ITM2A, a transcriptional target of PKA-CREB, regulates autophagic flux via interaction with the vacuolar ATPase

Namkoong

Lee

et al. 2015

Autophagy

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Abbreviations: BafA1, bafilomycin A 1 ; cAMP, cyclic adenosine monophosphate; ChIP, chromatin immunoprecipitation; CRE, cAMP response element; CREB, cAMP responsive element binding protein; EBSS, Earle's balanced salt solution; ITM2A, integral membrane protein 2A; LAMP1, lysosomal-associated membrane protein 1; MAP1LC3B/LC3B, microtubule-associated protein 1 light chain 3 b; MAPK, mitogen-activated protein kinase; MTOR, mechanistic target of rapamycin; PKA, protein kinase A; SQSTM1, sequestosome 1; tfLC3, tandem fluorescent-tagged LC3; TPA, 12-O-tetradecanoylphorbol-13-acetate; v-ATPase, vacuolar ATPase.The PKA-CREB signaling pathway is involved in many cellular processes including autophagy. Recent studies demonstrated that PKA-CREB inhibits autophagy in yeast; however, the role of PKA-CREB signaling in mammalian cell autophagy has not been fully characterized. Here, we report that the integral membrane protein ITM2A expression is positively regulated by PKA-CREB signaling and ITM2A expression interferes with autophagic flux by interacting with vacuolar ATPase (v-ATPase). The ITM2A promoter contains a CRE element, and mutation at the CRE consensus site decreases the promoter activity. Forskolin treatment and PKA expression activate the ITM2A promoter confirming that ITM2A expression is dependent on the PKA-CREB pathway. ITM2A expression results in the accumulation of autophagosomes and interferes with autolysosome formation by blocking autophagic flux. We demonstrated that ITM2A physically interacts with v-ATPase and inhibits lysosomal function. These results support the notion that PKA-CREB signaling pathway regulates ITM2A expression, which negatively regulates autophagic flux by interfering with the function of v-ATPase.

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Constitutive overexpression of the integral membrane protein Itm2A enhances myogenic differentiation of C2C12 cells

Cited by 27 publications

References 12 publications

Comparative analysis of genes regulated in acute myelomonocytic leukemia with and without inv(16)(p13q22) using microarray techniques, real-time PCR, immunohistochemistry, and flow cytometry immunophenotyping

Comparative analysis of genes regulated in acute myelomonocytic leukemia with and without inv(16)(p13q22) using microarray techniques, real-time PCR, immunohistochemistry, and flow cytometry immunophenotyping

Meta-analysis of differentially expressed genes in ankylosing spondylitis

The integral membrane protein ITM2A, a transcriptional target of PKA-CREB, regulates autophagic flux via interaction with the vacuolar ATPase

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