Abstract
Because heat shock factor 1 (HSF1) phosphorylation by Plk1 has been previously reported to be involved in mitotic regulation and p53 function may be involved in this mitotic regulation, we have further examined HSF1 functions in mitotic regulation according to p53 status. Nocodazole-mediated aneuploidy was increased in p53-defective (p53Mut) cells; however, it was not increased in p53 wild-type (p53WT) cells. Phosphorylation of HSF1 at Ser216 was increased in p53Mut cells with increased stability of securin and cyclin B1 in mitosis compared with p53WT cells. The interaction of p53 with Plk1 that was shown in p53WT cells and that induced normal mitotic checkpoint function was not observed in p53Mut cells; instead, the binding of HSF1 with Plk1 and HSF1 phosphorylation at Ser216 were seen in p53Mut cells, which resulted in increased aneuploidy production. Moreover, the interaction affinity of Cdc20 with Mad2 was inhibited in p53Mut cells, whereas the interaction between Cdc20 and HSF1 was increased. From the data, it was suggested that HSF1-mediated aneuploidy was more facilitated in p53-defective cells, indicating the importance of novel mechanisms for p53 function in HSF1-mediated mitotic regulation and genomic instability.
| Original language | English |
|---|---|
| Pages (from-to) | 9404-9412 |
| Number of pages | 9 |
| Journal | Cancer Research |
| Volume | 69 |
| Issue number | 24 |
| DOIs | |
| Publication status | Published - 2009 Dec 15 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Heat shock factor 1-mediated aneuploidy requires a defective function of p53. / Kim, Eun Ho; Lee, Yoon Jin; Bae, Sangwoo; Lee, Jae Seon; Kim, Joon; Lee, Yun Sil.
In: Cancer Research, Vol. 69, No. 24, 15.12.2009, p. 9404-9412.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Heat shock factor 1-mediated aneuploidy requires a defective function of p53
AU - Kim, Eun Ho
AU - Lee, Yoon Jin
AU - Bae, Sangwoo
AU - Lee, Jae Seon
AU - Kim, Joon
AU - Lee, Yun Sil
PY - 2009/12/15
Y1 - 2009/12/15
N2 - Because heat shock factor 1 (HSF1) phosphorylation by Plk1 has been previously reported to be involved in mitotic regulation and p53 function may be involved in this mitotic regulation, we have further examined HSF1 functions in mitotic regulation according to p53 status. Nocodazole-mediated aneuploidy was increased in p53-defective (p53Mut) cells; however, it was not increased in p53 wild-type (p53WT) cells. Phosphorylation of HSF1 at Ser216 was increased in p53Mut cells with increased stability of securin and cyclin B1 in mitosis compared with p53WT cells. The interaction of p53 with Plk1 that was shown in p53WT cells and that induced normal mitotic checkpoint function was not observed in p53Mut cells; instead, the binding of HSF1 with Plk1 and HSF1 phosphorylation at Ser216 were seen in p53Mut cells, which resulted in increased aneuploidy production. Moreover, the interaction affinity of Cdc20 with Mad2 was inhibited in p53Mut cells, whereas the interaction between Cdc20 and HSF1 was increased. From the data, it was suggested that HSF1-mediated aneuploidy was more facilitated in p53-defective cells, indicating the importance of novel mechanisms for p53 function in HSF1-mediated mitotic regulation and genomic instability.
AB - Because heat shock factor 1 (HSF1) phosphorylation by Plk1 has been previously reported to be involved in mitotic regulation and p53 function may be involved in this mitotic regulation, we have further examined HSF1 functions in mitotic regulation according to p53 status. Nocodazole-mediated aneuploidy was increased in p53-defective (p53Mut) cells; however, it was not increased in p53 wild-type (p53WT) cells. Phosphorylation of HSF1 at Ser216 was increased in p53Mut cells with increased stability of securin and cyclin B1 in mitosis compared with p53WT cells. The interaction of p53 with Plk1 that was shown in p53WT cells and that induced normal mitotic checkpoint function was not observed in p53Mut cells; instead, the binding of HSF1 with Plk1 and HSF1 phosphorylation at Ser216 were seen in p53Mut cells, which resulted in increased aneuploidy production. Moreover, the interaction affinity of Cdc20 with Mad2 was inhibited in p53Mut cells, whereas the interaction between Cdc20 and HSF1 was increased. From the data, it was suggested that HSF1-mediated aneuploidy was more facilitated in p53-defective cells, indicating the importance of novel mechanisms for p53 function in HSF1-mediated mitotic regulation and genomic instability.
UR - http://www.scopus.com/inward/record.url?scp=73649142444&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=73649142444&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-09-1411
DO - 10.1158/0008-5472.CAN-09-1411
M3 - Article
C2 - 19934326
AN - SCOPUS:73649142444
VL - 69
SP - 9404
EP - 9412
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 24
ER -