BM88/Cend1 is involved in histone deacetylase inhibition‐mediated growth arrest and differentiation of neuroblastoma cells

Abstract

Histone deacetylase inhibitors arrest the growth of neuroblastoma cells and induce differentiation. Identification of target genes that co-ordinate and mediate these effects is important for understanding the function of this novel class of antitumour drugs. We report here that trichostatin-A (TSA) specifically induces the transcription of Cend1, a neuronal-lineage specific regulator of cell cycle exit and differentiation, in neuroblastoma Neuro2A cells, but not in non-neuronal cells. Furthermore, we show that knockdown of Cend1 alleviates both the anti-proliferative and differentiation effect of TSA. Our findings suggest that Cend1 is an important molecular target for HDAC inhibition.

Putting the ‘HAT’ back on survival signalling: the promises and challenges of HDAC inhibition in the treatment of neurological conditions

“…The findings of studies by Vecsey et al [29], Kanai et al [30], Leng et al [31], and Politis et al [32] are consistent with the idea that multiple downstream gene targets contribute to the neuroprotective effects of HDAC inhibitor treatment. Vescey et al reported that HDAC inhibitors enhance memory by activating genes regulated by the CREB and CBP/HAT complex [29].…”

“…A study published by Leng et al , on the other hand, highlights the role of glycogen synthase kinase-3 inhibition and increased β-catenin-dependent and TCF-1/LEF-1-dependent gene expression–through combined treatment with lithium and an HDAC inhibitor (VPA, SPB, SB or TSA)–in protecting aging cerebellar granule cells against glutamate-induced cell death [31]. Finally, Politis et al showed that HDAC inhibition causes growth arrest and induces differentiation in neuroblastoma cells [32]. The authors identified Cend1 , a neuronal lineage-specific cell-cycle-exit molecule, as one of the genes mediating the function of HDAC inhibitors.…”

Functional Interactions between BM88/Cend1, Ran-Binding Protein M and Dyrk1B Kinase Affect Cyclin D1 Levels and Cell Cycle Progression/Exit in Mouse Neuroblastoma Cells

“…We have previously shown that overexpression of Cend1 in Neuro 2a cells results in attenuation of their proliferation accompanied by a reduction in cyclin D1 levels while the opposite is observed upon Cend1 knock-down [12,46]. To gain insight into the consequences of Cend1 interaction with RanBPM in this system, Neuro 2a cells were transiently transfected with plasmids for expression of Cend1 or RanBPM or both, at a ratio of 1:1, as well as with an empty vector.…”

Prox1 Regulates the Notch1-Mediated Inhibition of Neurogenesis

“…Transient transfections and luciferace reporter assays were performed with Lipofectamine (Invitrogen) and luciferase/β-galactosidase kits (Promega), respectively, as previously described [67],[68]. For Notch1-luc, Hes1-luc, Hes5-luc, and TK-luc constructs we have used 0.4 µg per transfection and 1.6 µg of expression vectors ( Prox1 , NR5A2 , or HDAC3 ).…”