The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function by Mediating the Ubiquitylation and Proteasomal Degradation of Survivin.

The Journal of Biological Chemistry
Yuan LiuRama K Mallampalli

Abstract

Fbxl7, a component of the Skp1·Cul1·F-box protein type ubiquitin E3 ligase, regulates mitotic cell cycle progression. Here we demonstrate that overexpression of Fbxl7 in lung epithelia decreases the protein abundance of survivin, a member of the inhibitor of apoptosis family. Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin by interacting with Glu-126 within its carboxyl-terminal α helix. Furthermore, both Lys-90 and Lys-91 within survivin serve as ubiquitin acceptor sites. Ectopically expressed Fbxl7 impairs mitochondrial function, whereas depletion of Fbxl7 protects mitochondria from actions of carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of oxidative phosphorylation. Compared with wild-type survivin, cellular expression of a survivin mutant protein deficient in its ability to interact with Fbxl7 (E126A) and a ubiquitylation-resistant double point mutant (KK90RR/KK91RR) rescued mitochondria to a larger extent from damage induced by overexpression of Fbxl7. Therefore, these data suggest that the Skp1·Cul1·F-box protein complex subunit Fbxl7 modulates mitochondrial function by controlling the cellular abundance of survivin. The results raise opportunities for F-box protein targeting to preserv...Continue Reading

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Citations

Sep 30, 2015·Seminars in Cancer Biology·Suzanne J Randle, Heike Laman
Oct 3, 2015·Seminars in Cancer Biology·Yuan Liu, Rama K Mallampalli
Feb 28, 2019·The Cerebellum·Jerry Vriend, Robert B Tate
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Dec 10, 2019·Cell Biology International·Akshay Sharma, Arun K Trivedi
Mar 10, 2020·Journal of Cellular and Molecular Medicine·Shiqi KongZongmao Zhao
Sep 26, 2019·Cell Death & Disease·Xiaotian SunLloyd A Greene
Dec 19, 2019·Frontiers in Oncology·Xing-Wei NanXiao-Jian Yan
Jan 17, 2019·Clinical and Translational Allergy·Ozlem KeskinOmer Kalayci
Jan 29, 2020·JCI Insight·Yao TongBill B Chen
Jan 15, 2021·Scientific Reports·Marianna MiliarakiGeorge Briassoulis
Jan 27, 2021·Nature Chemical Biology·Yuan LiuRama K Mallampalli
Mar 19, 2021·Cell & Bioscience·Qiyin ZhouYi Sun
Aug 27, 2021·Biochemical and Biophysical Research Communications·Wei WangLisheng Li

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