Send to:

Choose Destination
See comment in PubMed Commons below
Cell Signal. 2009 May;21(5):801-9. Epub 2009 Jan 20.

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

Author information

  • 1Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell'Apparato Locomotore, Cell Signalling Laboratory, Universit√† di Bologna, via Irnerio 48, 40126 Bologna, Italy.


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.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Loading ...
    Write to the Help Desk