HDAC and Hsp90 inhibitors down-regulate PTTG1/securin but do not induce aneuploidy.
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 > or =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.
Hernández
Agustín
A
Cell Signaling Department, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER-CSIC), Avda. Américo Vespucio s/n, Seville, Spain. ahernan@cica.es
López-Lluch
Guillermo
G
Navas
Plácido
P
Pintor-Toro
José A
JA
D000782:Aneuploidy; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D016193:G1 Phase / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D064249:Securin
D018841:HSP90 Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D006655:Histone Deacetylases