TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-ζ-dependent cell cycle arrest

Camilla Evangelisti, Annalisa Astolfi, Gian Carlo Gaboardi, Pierluigi Tazzari, Andrea Pession, Kaoru Goto, Alberto M. Martelli

Research output: Contribution to journalArticle

23 Citations (Scopus)

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-ζ negatively regulates cell cycle progression. The aim of this study was to identify key determinants of nuclear DGK-ζ-dependent cell cycle arrest in C2C12 mouse myoblasts. Using DNA microarrays, Real-Time RT-PCR and western blot, we demonstrated that nuclear DGK-ζ 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-ζ. 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-ζ and highlight the importance of this DGK isoform in the regulation of myoblast proliferation and differentiation.

Original languageEnglish
Pages (from-to)801-809
Number of pages9
JournalCellular Signalling
Volume21
Issue number5
DOIs
Publication statusPublished - May 2009

Fingerprint

Diacylglycerol Kinase
Cyclin D1
Cell Cycle Checkpoints
Myoblasts
Second Messenger Systems
Cell Cycle
Down-Regulation
Lipids
Retinoblastoma Protein
Diglycerides
G1 Phase
Oligonucleotide Array Sequence Analysis
Small Interfering RNA
Real-Time Polymerase Chain Reaction
Cell Differentiation
Protein Isoforms
Western Blotting
Cell Membrane

Keywords

  • Diacylglycerol
  • Differentiation
  • Lipid signaling
  • Nucleus
  • Proliferation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Evangelisti, C., Astolfi, A., Gaboardi, G. C., Tazzari, P., Pession, A., Goto, K., & Martelli, A. M. (2009). TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-ζ-dependent cell cycle arrest. Cellular Signalling, 21(5), 801-809. https://doi.org/10.1016/j.cellsig.2009.01.027

TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-ζ-dependent cell cycle arrest. / Evangelisti, Camilla; Astolfi, Annalisa; Gaboardi, Gian Carlo; Tazzari, Pierluigi; Pession, Andrea; Goto, Kaoru; Martelli, Alberto M.

In: Cellular Signalling, Vol. 21, No. 5, 05.2009, p. 801-809.

Research output: Contribution to journalArticle

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-ζ-dependent cell cycle arrest', Cellular Signalling, vol. 21, no. 5, pp. 801-809. https://doi.org/10.1016/j.cellsig.2009.01.027
Evangelisti, Camilla ; Astolfi, Annalisa ; Gaboardi, Gian Carlo ; Tazzari, Pierluigi ; Pession, Andrea ; Goto, Kaoru ; Martelli, Alberto M. / TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-ζ-dependent cell cycle arrest. In: Cellular Signalling. 2009 ; Vol. 21, No. 5. pp. 801-809.
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