http://www.cnr.it/ontology/cnr/individuo/prodotto/ID27585

TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-zeta-dependent cell cycle arrest. (Articolo in rivista)

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TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-zeta-dependent cell cycle arrest. (Articolo in rivista) (literal)

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Evangelisti C, Astolfi A, Gaboardi GC, Tazzari P, Pession A, Goto K, Martelli AM. (2009)
TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-zeta-dependent cell cycle arrest.
in Cellular signalling
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Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Evangelisti C, Astolfi A, Gaboardi GC, Tazzari P, Pession A, Goto K, Martelli AM. (literal)

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Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell'Apparato Locomotore, Cell Signalling Laboratory, Università di Bologna, via Irnerio 48, 40126 Bologna, Italy; Unità di Oncologia ed Ematologia Pediatrica Lalla Seràgnoli, Università di Bologna, Policlinico S. Orsola-Malpighi, via Massarenti 9, 40138 Bologna, Italy; Servizio di Immunoematologia e Trasfusionale, Policlinico S.Orsola-Malpighi, via Massarenti 9, 40138 Bologna, Italy; Department of Anatomy and Cell Biology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan; Istituto di Genetica Molecolare del Consiglio Nazionale delle Ricerche, c/o Istituto Ortopedico Rizzoli, via di Barbiano 1/10, 40136 Bologna, Italy (literal)

Titolo

TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-zeta-dependent cell cycle arrest. (literal)

Abstract

In addition to lipid second messengers derived from the plasma membrane, increasing evidence supports the existence of nuclear lipid-dependent signaling networks. Diacylglycerol is a key second messenger, generated at the nuclear level, which is metabolized by diacylglycerol kinases (DGKs). It has been demonstrated that nuclear DGK-zeta negatively regulates cell cycle progression. The aim of this study was to identify key determinants of nuclear DGK-zeta-dependent cell cycle arrest in C2C12 mouse myoblasts. Using DNA microarrays, Real-Time RT-PCR and western blot, we demonstrated that nuclear DGK-zeta downregulated the expression of cyclin D1 and increased the expression of TIS21/BTG2/PC3, a transcriptional regulator of cyclin D1 with a strong anti-proliferative function. Overexpression of TIS21/BTG2/PC3 blocked the cells in G1 phase of the cell cycle and decreased the levels of Ser807/811 phosphorylated retinoblastoma protein, similarly to overexpression of DGK-zeta. Moreover, during myogenic differentiation of C2C12 cells, we showed an increase of TIS21/BTG2/PC3 expression and a decrease in cyclin D1 levels. siRNA downregulation of TIS21/ BTG2/PC3 impaired myogenic differentiation by opposing cell cycle arrest. In summary, these data identify TIS21/BTG2/PC3 and cyclin D1 as downstream effectors of nuclear DGK-zeta and highlight the importance of this DGK isoform in the regulation of myoblast proliferation and differentiation. (literal)

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