EPLIN, Epithelial protein lost in neoplasm

Maul, Raymond Scott; Chang, David D.

doi:10.1038/sj.onc.1203206

Cited by 87 publications

(183 citation statements)

References 17 publications

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“…Several cancer genes reside in the loss, including the LIMA1 putative tumor suppressor gene. 22 The ANP32D and LETMD1 genes, also present within the consensus region of loss, are oncogenic. DUSP6, another candidate tumor suppressor gene within the LOH consensus deletion loci, is located outside the array CGH defined MCRs on 12q that is reported here.…”

Section: Discussionmentioning

confidence: 99%

High-resolution array comparative genomic hybridization analysis of human bronchial and salivary adenoid cystic carcinoma

Bernheim

Toujani

Saulnier

et al. 2008

Laboratory Investigation

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Adenoid cystic carcinoma (ACC) is a rare but distinctive tumor. Oligonucleotide array comparative genomic hybridization has been applied for cataloging genomic copy number alterations (CNAs) in 17 frozen salivary or bronchial tumors. Only four whole chromosome CNAs were found, and most cases had 2-4 segmental CNAs. No high level amplification was observed. There were recurrent gains at 7p15.2, 17q21-25, and 22q11-13, and recurrent losses at 1p35, 6q22-25, 8q12-13, 9p21, 12q12-13, and 17p11-13. The minimal region of gain at 7p15.2 contained the HOXA cluster. The minimal common regions of deletions contained the CDKN2A/CDKN2B, TP53, and LIMA1 tumor suppressor genes. The recurrent deletion at 8q12.3-13.1 contained no straightforward tumor suppressor gene, but the MIRN124A2 microRNA gene, whose product regulates MMP2 and CDK6. Among unique CNAs, gains harbored CCND1, KIT/PDGFRA/KDR, MDM2, and JAK2. The CNAs involving CCND1, MDM2, KIT, CDKN2A/2B, and TP53 were validated by FISH and/or multiplex ligation-dependent probe amplification. Although most tumors overexpressed cyclin D1 compared with surrounding glands, the only case to overexpress MDM2 had the corresponding CNA. In conclusion, our report suggests that ACC is characterized by a relatively low level of structural complexity. Array CGH and immunohistochemical data implicate MDM2 as the oncogene targeted at 12q15. The gain at 4q12 warrants further exploration as it contains a cluster of receptor kinase genes (KIT/PDGFRA/KDR), whose products can be responsive to specific therapies.

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Section: Discussionmentioning

confidence: 99%

High-resolution array comparative genomic hybridization analysis of human bronchial and salivary adenoid cystic carcinoma

Bernheim

Toujani

Saulnier

et al. 2008

Laboratory Investigation

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“…In addition, some LIM domain-containing proteins are also involved in pathological processes such as oncogenesis (e.g. EPLIN, Testin and LMO4) (Maul and Chang, 1999;Tatarelli et al, 2000;Tobias et al, 2001;Visvader et al, 2001;Song et al, 2002;Sum et al, 2002;Garvalov et al, 2003). As the full-length ZNF185 cDNA has not been experimentally cloned, the biological function of this LIM domain-containing protein and the pathological relevance in PCa is unknown.…”

Section: Introductionmentioning

confidence: 99%

ZNF185, an actin–cytoskeleton-associated growth inhibitory LIM protein in prostate cancer

2006

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We have recently identified ZNF185 as a gene that is downregulated in prostate cancer (PCa), in part via epigenetic alteration, and maybe associated with disease progression. In this study, we cloned the ZNF185 cDNA from normal human prostate tissues and investigated its biological function. We show that ZNF185 is a novel actin-cytoskeleton-associated Lin-l 1, Isl-1 and Mec-3 (LIM) domain-containing protein that localizes to F-actin structures, and is enriched at focal adhesions. We find that the NH 2 -terminal region, which we designate the actintargeting domain, facilitates ZNF185 binding to actin in vitro and is both necessary and sufficient to mediate actin-cytoskeleton targeting of ZNF185, whereas the LIM domain, which is localized in the COOH-terminus is dispensable for this phenomenon. Interestingly, ectopic expression of full-length ZNF185, but not a mutant lacking the actin-targeting domain, could suppress proliferation and anchorage-independent growth of PCa cells. Together, our data suggest that ZNF185 may function as a tumor-suppressor protein by associating with the actincytoskeleton.

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“…LIMA1 is a cytoskeleton-associated protein encoded by a gene on band 12q13 and contains a single centrally located lin-11, isl-1 and mec-3 (LIM) domain, flanked by two actin-binding domains each located at the N-and C termini of the wild-type protein 58 . LIMA1 has been recognized as a tumour suppressor based on the multiple mechanisms by which it is targeted for inactivation 40,42,44,59 . LIMA1 protein is preferentially expressed in human epithelial cells and has been observed to be transcriptionally downregulated in epithelial malignancies 40 .…”

Section: Discussionmentioning

confidence: 99%

“…LIMA1 has been recognized as a tumour suppressor based on the multiple mechanisms by which it is targeted for inactivation 40,42,44,59 . LIMA1 protein is preferentially expressed in human epithelial cells and has been observed to be transcriptionally downregulated in epithelial malignancies 40 .…”

Section: Discussionmentioning

confidence: 99%

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Conversion of the LIMA1 tumour suppressor into an oncogenic LMO-like protein by API2–MALT1 in MALT lymphoma

Nie

McAllister-Lucas

et al. 2015

Nat Commun

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MALT1 is the only known paracaspase and is a critical mediator of B-and T-cell receptor signalling. The function of the MALT1 gene is subverted by oncogenic chimeric fusions arising from the recurrent t(11;18)(q21;q21) aberration, which is the most frequent translocation in mucosa-associated lymphoid tissue (MALT) lymphoma. API2-MALT1-positive MALT lymphomas manifest antibiotic resistance and aggressive clinical behaviour with poor clinical outcome. However, the mechanisms underlying API2-MALT1-induced MALT lymphomagenesis are not fully understood. Here we show that API2-MALT1 induces paracaspase-mediated cleavage of the tumour suppressor protein LIMA1. LIMA1 binding by API2-MALT1 is API2 dependent and proteolytic cleavage is dependent on MALT1 paracaspase activity. Intriguingly, API2-MALT1-mediated proteolysis generates a LIM domain-only (LMO)-containing fragment with oncogenic properties in vitro and in vivo. Importantly, primary MALT lymphomas harbouring the API2-MALT1 fusion uniquely demonstrate LIMA1 cleavage fragments. Our studies reveal a novel paracaspase-mediated oncogenic gain-of-function mechanism in the pathogenesis of MALT lymphoma.

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EPLIN, Epithelial protein lost in neoplasm

Cited by 87 publications

References 17 publications

High-resolution array comparative genomic hybridization analysis of human bronchial and salivary adenoid cystic carcinoma

High-resolution array comparative genomic hybridization analysis of human bronchial and salivary adenoid cystic carcinoma

ZNF185, an actin–cytoskeleton-associated growth inhibitory LIM protein in prostate cancer

Conversion of the LIMA1 tumour suppressor into an oncogenic LMO-like protein by API2–MALT1 in MALT lymphoma

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