In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 69, No. 3 ( 2009-02-01), p. 741-746
Abstract:
The p34SEI-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 p34SEI-1 increases tumor cell survival by protecting the X-linked inhibitor of apoptosis protein (XIAP) from degradation. Our findings show that p34SEI-1 inhibits apoptosis. This antiapoptotic effect was eliminated by the suppression of p34SEI-1 expression. We also determined that direct binding of p34SEI-1 to the BIR2 domain prevents ubiquitination of XIAP. Interestingly, p34SEI-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 p34SEI-1 and XIAP seem to be coordinated in human breast cancer cell lines and tumor tissues. Thus, our findings reveal that p34SEI-1 uses a novel apoptosis-inhibiting mechanism to stabilize XIAP. [Cancer Res 2009;69(3):741–6]
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-08-1189
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2009
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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