Temporal and spatial expression profile of the novelarmadillo-related gene,Alex2, during testicular differentiation in the mouse embryo

Smith, Craig A.; McClive, Peter J.; Sinclair, Andrew H.

doi:10.1002/dvdy.20309

Cited by 16 publications

(11 citation statements)

References 69 publications

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“…1C). This gene, ARMCX3, is a member of the ARMCX gene family about which little is known functionally (32)(33)(34). Direct interaction between Sox10 and ARMCX3 was confirmed by co-transfection of pACT2-ARMCX3 and pGBKT7-Sox10N100 in the yeast strain AH109 and subsequent growth on strict selection plates (data not shown).…”

Section: Resultsmentioning

confidence: 92%

The Armadillo Repeat-containing Protein, ARMCX3, Physically and Functionally Interacts with the Developmental Regulatory Factor Sox10

Mou

Tapper

Gardner

2009

Journal of Biological Chemistry

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Sox10 is a member of the group E Sox transcription factor family and plays key roles in neural crest development and subsequent cellular differentiation. Sox10 binds to regulatory sequences in target genes via its conserved high mobility group domain. In most cases, Sox10 exerts its transcriptional effects in concert with other DNA-binding factors, adaptor proteins, and nuclear import proteins. These interactions can lead to synergistic gene activation and can be cell type-specific. In earlier work, we demonstrated that Sox10 transactivates the nicotinic acetylcholine receptor ␣3 and ␤4 subunit genes and does so only in neuronal-like cell lines, raising the possibility that Sox10 mediates its effects via interactions with co-regulatory factors. Here we describe the identification of the armadillo repeat-containing protein, ARMCX3, as a Sox10-interacting protein. Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane. Others have shown that Sox10 is a nucleocytoplasmic shuttling protein. We extend this observation and demonstrate that, in the cytoplasm, Sox10 is peripherally associated with the mitochondrial outer membrane. Both Sox10 and ARMCX3 are expressed in mouse brain and spinal cord as well as several cell lines. Overexpression of ARMCX3 increased the amount of mitochondrially associated Sox10. In addition, although ARMCX3 does not possess intrinsic transcriptional activity, it does enhance transactivation of the nicotinic acetylcholine receptor ␣3 and ␤4 subunit gene promoters by Sox10. These results suggest that Sox10 is a membrane-associated factor whose transcriptional function is increased by direct interactions with ARMCX3 and raise the possibility of a signal transduction cascade between the nucleus and mitochondria through Sox10/ARMCX3 interactions.

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Section: Resultsmentioning

confidence: 92%

The Armadillo Repeat-containing Protein, ARMCX3, Physically and Functionally Interacts with the Developmental Regulatory Factor Sox10

Mou

Tapper

Gardner

2009

Journal of Biological Chemistry

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“…However, little is known about the function in drug resistance of the other genes found to commonly acquire methylation in tumours and cell lines at relapse and in drug-resistant SP populations. ARMCX2 might have a role in tumour suppression based on the presence of an armadillo repeat motif, which is found in other proteins fulfilling functions in cell proliferation, migration, maintenance of tissue integrity and tumourigenesis, and has been involved in development (Smith et al, 2005). MEST, a maternally imprinted gene, has been implicated in embryonic growth and maternal behaviour (Lefebvre et al, 1998), and loss of MEST imprinting has been reported in breast and lung cancers (Pedersen et al, 2002;Nakanishi et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling

et al. 2012

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Multiple DNA methylation changes in the cancer methylome are associated with the acquisition of drug resistance; however it remains uncertain how many represent critical DNA methylation drivers of chemoresistance. Using isogenic, cisplatin-sensitive/resistant ovarian cancer cell lines and inducing resensitizaton with demethylating agents, we aimed to identify consistent methylation and expression changes associated with chemoresistance. Using genome-wide DNA methylation profiling across 27 578 CpG sites, we identified loci at 4092 genes becoming hypermethylated in chemoresistant A2780/cp70 compared with the parental-sensitive A2780 cell line. Hypermethylation at gene promoter regions is often associated with transcriptional silencing; however, expression of only 245 of these hypermethylated genes becomes downregulated in A2780/cp70 as measured by microarray expression profiling. Treatment of A2780/ cp70 with the demethylating agent 2-deoxy-5 0 -azacytidine induces resensitization to cisplatin and re-expression of 41 of the downregulated genes. A total of 13/41 genes were consistently hypermethylated in further independent cisplatin-resistant A2780 cell derivatives. CpG sites at 9 of the 13 genes (ARHGDIB, ARMCX2, COL1A, FLNA, FLNC, MEST, MLH1, NTS and PSMB9) acquired methylation in ovarian tumours at relapse following chemotherapy or chemoresistant cell lines derived at the time of patient relapse. Furthermore, 5/13 genes (ARMCX2, COL1A1, MDK, MEST and MLH1) acquired methylation in drug-resistant ovarian cancersustaining (side population) cells. MLH1 has a direct role in conferring cisplatin sensitivity when reintroduced into cells in vitro. This combined genomics approach has identified further potential key drivers of chemoresistance whose expression is silenced by DNA methylation that should be further evaluated as clinical biomarkers of drug resistance.

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“…Arm protein lost in epithelial cancers, on chromosome X ( ALEX ; also known as armadillo repeat containing, X‐linked [ ARMCX ]) is a novel subgroup within the ARM family. The ALEX/ARMCX gene family consists of six genes including three predicted genes ( ALEX1‐6 ) . Bioinformatics analyses suggest that the ALEX1 , ALEX2 and ALEX3 are each encoded by a single exon and contain an N‐terminal transmembrane domain, some ARM repeat domains, and a DUF634 (domain of unknown function 634) .…”

mentioning

confidence: 99%

“…In addition, gene expression analysis revealed that both ALEX1 and ALEX2 mRNA is expressed in a variety of adult human tissues, including colon, but dramatically reduced or even undetectable in several human carcinoma cell lines and tissues . In mouse embryos, ALEX2 mRNA is expressed in the developing testis, forebrain and somites, and in dorsal root ganglia and ribs . In vivo RNAi screening for potential tumor suppressor genes using immortalized embryonic hepatocytes lacking p53 and overexpressing MYC revealed that knockdown of ALEX1 and ALEX2 individually accelerated hepatocarcinogenesis in mice .…”

mentioning

confidence: 99%

ALEX1 suppresses colony formation ability of human colorectal carcinoma cell lines

et al. 2012

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Arm protein lost in epithelial cancers, on chromosome X (ALEX; also known as armadillo repeat containing, X-linked [ARMCX]) is a novel subgroup within the armadillo (ARM) family, which has several ARM repeat domains. The biological function of classical ARM family members such as b-catenin is well understood, but that of the ALEX/ARMCX family members is largely unknown. Here we evaluate the effects of ALEX1 overexpression on in vitro colony formation ability and expression of ALEX1 mRNA in human colorectal tumor. Overexpression of ALEX1 suppressed the anchorage-dependent and -independent colony formation of human colorectal carcinoma cell lines by the study of stable clones of HCT116 cells expressing ALEX1 protein. Bisulfite genomic sequencing revealed that the promoter region of ALEX1 gene was highly methylated in both HCT116 and SW480 cells in comparison with PANC-1 and MCF-7 cells, which express endogenous ALEX1 mRNA, indicating the capability of promoter methylation to silence ALEX1 gene in HCT116 and SW480 cells. Our current findings suggest that overexpression of ALEX1 play a negative role in human colorectal tumorigenesis. (Cancer Sci 2012; 103: 1267-1271 A rmadillo (ARM) repeat proteins, characterized by the presence of a repeating 42 amino acid motif, form a large family implicated in a variety of processes such as cell adhesion, embryogenesis and tumorigenesis.(1,2) Armadillo repeats mediate protein-protein interaction with diverse binding partners involved in cell junction assembly, nuclear transport and transcription activation.(3-5) b-Catenin (CTNND1 gene), a classical member of ARM family, is a multifunctional protein that plays essential roles both at adherence junctions and in Wnt signaling through interaction with E-cadherin and T cell factor/lymphoid enhancer factor (TCF/LEF) family transcription factors, respectively.(6,7) Tumor suppressor adenomatous polyposis coli (APC) is also an ARM family member and acts synergistically with casein kinase Ι, glycogen synthase kinase-3b and AXIN to regulate Wnt signaling via b-catenin degradation.(8-10) Approximately 80% of the sporadic colorectal carcinomas have inactivating mutations in APC and degradation-resistant mutations in b-catenin occur in around 50% of the remaining colorectal carcinomas. These mutations can cause aberrant nuclear accumulation of b-catenin, leading to the transcriptional activation of the Wnt target genes such as oncogenic c-MYC and CCND1. (8,9,(11)(12)(13) Arm protein lost in epithelial cancers, on chromosome X (ALEX; also known as armadillo repeat containing, X-linked [ARMCX]) is a novel subgroup within the ARM family. The ALEX/ARMCX gene family consists of six genes including three predicted genes (ALEX1-6).(14-16) Bioinformatics analyses suggest that the ALEX1, ALEX2 and ALEX3 are each encoded by a single exon and contain an N-terminal transmembrane domain, some ARM repeat domains, and a DUF634 (domain of unknown function 634).(14-16) However, little is known about the ALEX/ARMCX genes. The only report regarding the biologi...

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Temporal and spatial expression profile of the novelarmadillo-related gene,Alex2, during testicular differentiation in the mouse embryo

Cited by 16 publications

References 69 publications

The Armadillo Repeat-containing Protein, ARMCX3, Physically and Functionally Interacts with the Developmental Regulatory Factor Sox10

The Armadillo Repeat-containing Protein, ARMCX3, Physically and Functionally Interacts with the Developmental Regulatory Factor Sox10

Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling

ALEX1 suppresses colony formation ability of human colorectal carcinoma cell lines

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