SIRT2 downregulation confers resistance to microtubule inhibitors by prolonging chronic mitotic arrest.

We previously identified SIRT2, a deacetylase for tubulin and histone H4, as a protein downregulated in gliomas, and reported that exogenously-expressed SIRT2 arrests the cell cycle prior to entry into mitosis to prevent chromosomal instability in response to microtubule inhibitors (MTIs) such as nocodazole, characteristics previously reported for the CHFR protein. We herein investigated the effects of SIRT2 downregulation on sensitivity to MTIs using HCT116 cells, a mitotic checkpoint-proficient near-diploid cancer cell line used for studying checkpoints. We found that SIRT2 downregulation confers resistance to MTIs as well as that of BubR1, a well-characterized mitotic checkpoint protein, though by a different mechanism.

Introduction of a CD40L genomic fragment via a human artificial chromosome vector permits cell-type-specific gene expression and induces immunoglobulin secretion.

Gene therapy using cDNA driven by an exogenous promoter is not suited for genetic disorders that require intrinsic expression of a transgene, such as hyperimmunoglobulin (Ig)M syndrome (HIGM), which is caused by mutations in the CD40L gene. The human artificial chromosome (HAC) vector has the potential to solve this problem, because it can be used to transfer large genomic fragments containing their own regulatory elements. In this study, we examined whether introduction of a genomic fragment of CD40L via the HAC vector permits intrinsic expression of the transgene and has an effect on immunoglobulin secretion.