Evidence of key role of Cdk2 overexpression in pemphigus vulgaris

Alessandro Lanza, Nicola Cirillo, Raffaele Rossiello, Monica Rienzo, Luisa Cutillo, Amelia Casamassimi, Filomena De Nigris, Concetta Schiano, Luigi Rossiello, Felice Femiano, Fernando Gombos, Claudio Napoli

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The pathogenesis of pemphigus vulgaris (PV) is still poorly understood. Autoantibodies present in PV patients can promote detrimental effects by triggering altered transduction of signals, which results in a final acantholysis. To investigate mechanisms involved in PV, cultured keratinocytes were treated with PV serum. PV sera were able to promote the cell cycle progression, inducing the accumulation of cyclin-dependent kinase 2 (Cdk2). Microarray analysis on keratinocytes detected that PV serum induced important changes in genes coding for one and the same proteins with known biological functions involved in PV disease (560 differentially expressed genes were identified). Then, we used two different approaches to investigate the role of Cdk2. First, small interfering RNA depletion of Cdk2 prevented cell-cell detachment induced by PV sera. Second, pharmacological inhibition of Cdk2 activity through roscovitine prevented blister formation and acantholysis in the mouse model of the disease. In vivo PV serum was found to alter multiple different pathways by microarray analysis (1463 differentially expressed genes were identified). Major changes in gene expression induced by roscovitine were studied through comparison of effects of PV serum alone and in association with roscovitine. The most significantly enriched pathways were cell communication, gap junction, focal adhesion, adherens junction, and tight junction. Our data indicate that major Cdk2-dependent multiple gene regulatory events are present in PV. This alteration may influence the evolution of PV and its therapy.

Original languageEnglish
Pages (from-to)8736-8745
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number13
DOIs
Publication statusPublished - Mar 28 2008

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Cyclin-Dependent Kinase 2
Pemphigus
Genes
Microarrays
Serum
Acantholysis
Gene expression
Autoantibodies
Small Interfering RNA
Microarray Analysis
Keratinocytes
Adhesion
Cells
Association reactions
Communication
Adherens Junctions
Focal Adhesions
Tight Junctions
Gap Junctions
Blister

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Lanza, A., Cirillo, N., Rossiello, R., Rienzo, M., Cutillo, L., Casamassimi, A., ... Napoli, C. (2008). Evidence of key role of Cdk2 overexpression in pemphigus vulgaris. Journal of Biological Chemistry, 283(13), 8736-8745. https://doi.org/10.1074/jbc.M702186200

Evidence of key role of Cdk2 overexpression in pemphigus vulgaris. / Lanza, Alessandro; Cirillo, Nicola; Rossiello, Raffaele; Rienzo, Monica; Cutillo, Luisa; Casamassimi, Amelia; De Nigris, Filomena; Schiano, Concetta; Rossiello, Luigi; Femiano, Felice; Gombos, Fernando; Napoli, Claudio.

In: Journal of Biological Chemistry, Vol. 283, No. 13, 28.03.2008, p. 8736-8745.

Research output: Contribution to journalArticle

Lanza, A, Cirillo, N, Rossiello, R, Rienzo, M, Cutillo, L, Casamassimi, A, De Nigris, F, Schiano, C, Rossiello, L, Femiano, F, Gombos, F & Napoli, C 2008, 'Evidence of key role of Cdk2 overexpression in pemphigus vulgaris', Journal of Biological Chemistry, vol. 283, no. 13, pp. 8736-8745. https://doi.org/10.1074/jbc.M702186200
Lanza A, Cirillo N, Rossiello R, Rienzo M, Cutillo L, Casamassimi A et al. Evidence of key role of Cdk2 overexpression in pemphigus vulgaris. Journal of Biological Chemistry. 2008 Mar 28;283(13):8736-8745. https://doi.org/10.1074/jbc.M702186200
Lanza, Alessandro ; Cirillo, Nicola ; Rossiello, Raffaele ; Rienzo, Monica ; Cutillo, Luisa ; Casamassimi, Amelia ; De Nigris, Filomena ; Schiano, Concetta ; Rossiello, Luigi ; Femiano, Felice ; Gombos, Fernando ; Napoli, Claudio. / Evidence of key role of Cdk2 overexpression in pemphigus vulgaris. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 13. pp. 8736-8745.
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