p34SEI-1 inhibits apoptosis through the stabilization of the X-linked inhibitor of apoptosis protein: p34SEI-1 as a novel target for anti-breast cancer strategies.

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.
Mesh Terms:
Apoptosis, Breast Neoplasms, Cell Line, Tumor, Humans, Nuclear Proteins, Protein Binding, Protein Structure, Tertiary, RNA, Small Interfering, Trans-Activators, Transfection, Ubiquitin, X-Linked Inhibitor of Apoptosis Protein
Cancer Res.
Date: Feb. 01, 2009
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