Liu H.Peng H.-W.Cheng Y.-S.Yuan H.S.Yang-Yen H.-F.2019-07-222019-07-22200502707306https://scholars.lib.ntu.edu.tw/handle/123456789/414379https://www.scopus.com/inward/record.uri?eid=2-s2.0-16244384614&doi=10.1128%2fMCB.25.8.3117-3126.2005&partnerID=40&md5=ae48cd4d9bd8c3adf145a144c409bcc6Mcl-1 is one Bcl-2 family member that plays a pivotal role in animal development. The extremely labile nature of the Mcl-1 protein itself and the fact that the Mcl-1 level is a critical determinant in various cell survival pathways suggest that cellular processes that regulate Mcl-1 stability are as important as those that regulate Mcl-1 synthesis. Although transcriptional stimulation of Mcl-1 synthesis in response to various stimuli has been well documented, regulation of Mcl-1 stability has been hardly explored. In this study, we identified that the translationally controlled tumor protein (TCTP) was one cellular factor that interacted with Mcl-1 and modulated Mcl-1 stability. While overexpression of TCTP augmented the protein stability of Mcl-1, knockdown expression of TCTP by RNA interference destabilized Mcl-1. Furthermore, TCTP stabilized Mcl-1 through interfering with Mcl-1's degradation by the ubiquitin-dependent proteasome degradation pathway, and the TCTP binding-defective mutant of Mcl-1 (K257V) was much more susceptible to degradation and manifested a compromised antiapoptotic activity. Taken together, these results suggest that TCTP modulates Mcl-1's antiapoptotic activity by modulating its protein stability. The possible mechanism(s) involved in TCTP's modulation process is discussed. Copyright ? 2005, American Society for Microbiology. All Rights Reserved.proteasome; protein mcl 1; tumor protein; ubiquitin; animal cell; apoptosis; article; controlled study; gene mutation; gene overexpression; molecular stability; mouse; nonhuman; priority journal; protein degradation; protein interaction; protein stability; RNA interference; translation initiation; translation regulation; Amino Acid Sequence; Amino Acid Substitution; Animals; Apoptosis; Binding Sites; Cell Line; Down-Regulation; Lysine; Mice; Molecular Sequence Data; Mutation; Neoplasm Proteins; Proteasome Endopeptidase Complex; Protein Interaction Mapping; Proto-Oncogene Proteins c-bcl-2; RNA Interference; RNA, Small Interfering; Trans-Activation (Genetics); Tumor Markers, Biological; Two-Hybrid System Techniques; Ubiquitin; Animaliajournal article10.1128/MCB.25.8.3117-3126.2005https://www.scopus.com/inward/record.uri?eid=2-s2.0-16244384614&doi=10.1128%2fMCB.25.8.3117-3126.2005&partnerID=40&md5=ae48cd4d9bd8c3adf145a144c409bcc6157981982-s2.0-16244384614https://www.scopus.com/inward/record.uri?eid=2-s2.0-16244384614&doi=10.1128%2fMCB.25.8.3117-3126.2005&partnerID=40&md5=ae48cd4d9bd8c3adf145a144c409bcc6