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.
Hong
Seung-Woo
SW
Department of Anatomy and Tumor Immunity Medical Research Center, Division of Biological Sciences, Seoul National University College of Medicine, Sookmyung Women's University, Seoul, Korea.
Kim
Chang-Jae
CJ
Park
Won-Sang
WS
Shin
Jae-Sik
JS
Lee
Soon-Duck
SD
Ko
Seong-Gyu
SG
Jung
Sam-Il
SI
Park
In-Chul
IC
An
Sung-Kwan
SK
Lee
Won-Keun
WK
Lee
Wang-Jae
WJ
Jin
Dong-Hoon
DH
Lee
Myeong-Sok
MS
D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C402464:SERTAD1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025801:Ubiquitin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human