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-Woo; Kim, Chang-Jae; Park, Won-Sang; Shin, Jae-Sik; Lee, Soon-Duck; Ko, Seong-Gyu; Jung, Sam-Il; Park, In-Chul; An, Sung-Kwan; Lee, Won-Keun; Lee, Wang-Jae; Jin, Dong-Hoon; Lee, Myeong-Sok
- Issue Date
- Feb-2009
- Publisher
- AMER ASSOC CANCER RESEARCH
- Citation
- CANCER RESEARCH, v.69, no.3, pp 741 - 746
- Pages
- 6
- 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
1538-7445
- 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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