Differential expression of PDZ domain‐containing proteins in human diseases – challenging topics and novel issues

Facciuto, Florencia Natalia; Cavatorta, Ana Laura; Valdano, Marina Bugnon; Marziali, Federico; Gardiol, Daniela

doi:10.1111/j.1742-4658.2012.08699.x

Cited by 40 publications

(49 citation statements)

References 66 publications

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“…recruiting various molecules to the cell-cell contacts, and it is widely distributed at tight junctions in epithelial cells (44). Involvement of the airway epithelium is of importance in asthma pathogenesis because disruption of barrier functions could potentially lead to air pollution-related adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up

Gref¹,

Merid²,

Gruzieva³

et al. 2017

Am J Respir Crit Care Med

107

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up

Gref¹,

Merid²,

Gruzieva³

et al. 2017

Am J Respir Crit Care Med

107

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“…In several neoplastic lesions, tissue disorganization has been associated with alterations in DLG1 expression pattern (Facciuto et al, 2012). However, there are no data about possible changes in lesions associated with low-risk HPV, which, even linked to benign lesions which rarely progress to malignancy, cause cell hyperproliferation and aberrant differentiation (Jian et al, 1999;Cheng et al, 1995;McCord et al, 2014).…”

Section: Hpv-18 E7 Protein Induces An Increase In the Levels Of Dlg1mentioning

confidence: 99%

“…Several reports using human biopsies have described changes in DLG1 abundance and distribution during malignant progression (Facciuto et al, 2012). Interestingly, while a marked reduction of DLG1 levels in poorly differentiated tumours was described, overexpression and changes in DLG1 distribution at earlier stages of cervical, colon and breast cancers have been observed by different groups (Watson et al, 2002;Cavatorta et al, 2004;Fuja et al, 2004;Gardiol et al, 2006).…”

Section: Introductionmentioning

confidence: 98%

Disc large 1 expression is altered by human papillomavirus E6/E7 proteins in organotypic cultures of human keratinocytes

Valdano

Cavatorta

Morale

et al. 2016

Journal of General Virology

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Loss of cell polarity is a fundamental process in cell transformation. Among polarity proteins, we focused on human disc large (DLG1), which is localized mainly at adherens junctions and contributes to the control of cell proliferation. We previously demonstrated that its expression is altered in HPV-associated cervical neoplastic lesions, but the mechanisms beyond this remain unknown. In this study, we analysed the contribution of HPV proteins to the changes in DLG1 expression in the squamous epithelium. We observed tissue and intracellular misdistribution of DLG1 when high-risk HPV-18 E7 or E6/E7 proteins were expressed in organotypic raft cultures. The viral oncoproteins induce the loss of DLG1 from the cell borders and an increase in the level of DLG1 protein, reflecting the pattern observed in cervical lesions. These findings were corroborated in cultures bearing the entire HPV-18 genome. Interestingly, changes in tissue distribution and abundance of DLG1 were also detected in organotypic cultures expressing the low-risk HPV-11 E7 or E6/E7 proteins, suggesting a conserved function among different HPV types. However, for low-risk HPVs, the subcellular localization of DLG1 at cell-to-cell contacts was predominantly maintained. This report offers new evidence, we believe, of the involvement of HPV proteins in DLG1 expression pattern and our data support previous observations regarding DLG1 expression in cervical lesions.

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“…Several reports using human biopsies have described changes for DLG1 expression during malignant progression (Facciuto et al, 2012). While a marked reduction of DLG1 levels in later stages and in poorly differentiated tumours was described, a high overexpression and mislocalisation of DLG1 at earlier stages of cervical, colon, breast and gastric cancers was observed (Watson et al, 2002;Boussioutas et al, 2003;Cavatorta et al, 2004;Fuja et al, 2004;Gardiol et al, 2006).…”

Section: Introductionmentioning

confidence: 97%

Transcriptional and translational mechanisms contribute to regulate the expression of Discs Large 1 protein during different biological processes

Marziali

Cavatorta

Valdano

et al. 2015

Biological Chemistry

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Human discs large (DLG1) has been demonstrated to be involved in cell polarity and maintenance of tissue architecture. However, the mechanisms controlling DLG1 expression are not fully understood. This is relevant as DLG1 is lost during the later stages of malignant progression. We initiated a series of studies to analyse the mechanisms regulating DLG1 expression. We have previously reported the identification of an alternative splicing event in the 5' untranslated region (5'-UTR) of DLG1 mRNA that generates transcripts with two different 5'-UTR (short and large 5'-UTR variants). In this study, we further examined the impact of the DLG1 transcription and the role of the differential expression of the alternative 5'-UTRs on DLG1 protein levels. We analysed these mechanisms during cell processes like differentiation, cell cycle progression and cell-cell contact formation, where the importance of DLG1 activities was previously established. The data presented in this report suggest that the transcriptional regulation of DLG1 strongly contributes to DLG1 abundance and that differential expression of alternative 5'-UTRs with different translational properties, also cooperates, depending on the cell type and cell situation. This study provides new evidence for understanding the transcriptional regulation of DLG1 and the changes in DLG1 expression during different biological processes.

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Differential expression of PDZ domain‐containing proteins in human diseases – challenging topics and novel issues

Cited by 40 publications

References 66 publications

Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up

Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up

Disc large 1 expression is altered by human papillomavirus E6/E7 proteins in organotypic cultures of human keratinocytes

Transcriptional and translational mechanisms contribute to regulate the expression of Discs Large 1 protein during different biological processes

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