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HDAC and Hsp90 inhibitors down-regulate PTTG1/securin but do not induce aneuploidy

✍ Scribed by Agustín Hernández; Guillermo López-Lluch; Plácido Navas; José A. Pintor-Toro


Book ID
102221506
Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
223 KB
Volume
48
Category
Article
ISSN
1045-2257

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✦ Synopsis


Abstract

Human securin regulates correct chromatid separation. However, there are conflicting reports on the aneugenic effects of its gene deletion. Here we show that PTTG1/securin gene expression is dramatically repressed when Hsp90 or histone deacetylases are inhibited. However, these treatments do not increase the proportion of aneuploid cells. This was also confirmed using RNAi (silencing of PTTG1/securin ≥80%). As expected, histone deacetylases arrested cells in both G1 and G2. However, sec^−/−^ HCT116 cells showed a greater disposition to arrest cells in G2 than sec^+/+^ cells due to insufficient induction of CDKN1A. These results indicate that chromatid separation is controlled through redundant mechanisms and reveal a new aspect of securin in cell cycle regulation. © 2008 Wiley‐Liss, Inc.