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p34(SEI-1) Inhibits Apoptosis through the Stabilization of the X-Linked Inhibitor of Apoptosis Protein: p34(SEI-1) as a Novel Target for Anti-Breast Cancer Strategies

Authors
Hong, Seung-WooKim, Chang-JaePark, Won-SangShin, Jae-SikLee, Soon-DuckKo, Seong-GyuJung, Sam-IlPark, In-ChulAn, Sung-KwanLee, Won-KeunLee, Wang-JaeJin, Dong-HoonLee, Myeong-Sok
Issue Date
Feb-2009
Publisher
AMER ASSOC CANCER RESEARCH
Citation
CANCER RESEARCH, v.69, no.3, pp.741 - 746
Journal Title
CANCER RESEARCH
Volume
69
Number
3
Start Page
741
End Page
746
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13824
DOI
10.1158/0008-5472.CAN-08-1189
ISSN
0008-5472
Abstract
The p34(SEI-1) protein exerts oncogenic effects via regulation of the cell cycle, which occurs through a direct interaction with cyclin-dependent kinase 4. Such regulation can increase the survival of various types of tumor cells. Here, we show that the antiapoptotic function of p34(SEI-1) increases tumor cell survival by protecting the X-linked inhibitor of apoptosis protein (XIAP) from degradation. Our findings show that p34(SEI-1) inhibits apoptosis. This antiapoptotic effect was eliminated by the suppression of p34(SEI-1) expression. We also determined that direct binding of p34(SEI-1) to the BIR2 domain prevents ubiquitination of XIAP. Interestingly, p34(SEI-1) expression is absent or weak in normal tissues but is strongly expressed in tissues obtained from patients with breast cancer. Furthermore, the expression levels of p34(SEI-1) and XIAP seem to be coordinated in human breast cancer cell lines and tumor tissues. Thus, our findings reveal that p34(SEI-1) uses a novel apoptosis-inhibiting mechanism to stabilize XIAP. [Cancer Res 2009;69(3):741-6]
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