title: 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.
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.
authors.affiliation: 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.
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Hong
authors.forename: Chang-Jae
authors.initials: CJ
authors.lastname: Kim
authors.forename: Won-Sang
authors.initials: WS
authors.lastname: Park
authors.forename: Jae-Sik
authors.initials: JS
authors.lastname: Shin
authors.forename: Soon-Duck
authors.initials: SD
authors.lastname: Lee
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Ko
authors.forename: Sam-Il
authors.initials: SI
authors.lastname: Jung
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Park
authors.forename: Sung-Kwan
authors.initials: SK
authors.lastname: An
authors.forename: Won-Keun
authors.initials: WK
authors.lastname: Lee
authors.forename: Wang-Jae
authors.initials: WJ
authors.lastname: Lee
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Jin
authors.forename: Myeong-Sok
authors.initials: MS
authors.lastname: Lee
mesh_terms: 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*
chemical_list: 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