Survivin inhibits excessive autophagy in cancer cells but does so independently of its interaction with LC3

Humphry, Nicola J.; Wheatley, Sally P.

Abstract

Survivin expression is pivotal to life and death at the cellular level. For
the past decade its pro-survival activity has been attributed to its
essential role in cell proliferation and its ability to inhibit apoptosis.
However, a growing body of evidence suggests that it may also
contribute to cell viability through an as yet undefined role in
autophagy. We report that survivin overexpression in osteosarcoma
(U2OS) cells is associated with increased LC3-II expression, smaller
autophagosomes, enlarged lysosomes and reduced autophagic flux.
We also demonstrate that survivin binds LC3 directly through a
canonical LC3-interacting region (LIR) in its baculovirus inhibitors of
apoptosis protein (IAP) repeat BIR domain, mutation of which inhibits
the interaction, but does not abrogate its influence on autophagy.
Collectively these data suggest that survivin expression restricts
autophagic flux, thereby inhibiting late-stage autophagy and
preventing cell death, but does so independently of LC3.

Citation

Humphry, N. J., & Wheatley, S. P. (2018). Survivin inhibits excessive autophagy in cancer cells but does so independently of its interaction with LC3. Biology Open, 7(10), 037374. https://doi.org/10.1242/bio.037374

• Journal Article Type: Article
• Acceptance Date: Aug 23, 2018
• Online Publication Date: Oct 22, 2018
• Publication Date: Oct 15, 2018
• Deposit Date: Dec 10, 2018
• Publicly Available Date: Dec 10, 2018
• Journal: Biology Open
• Electronic ISSN: 2046-6390
• Publisher: Company of Biologists
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 10
• Pages: 037374
• DOI: https://doi.org/10.1242/bio.037374
• Public URL: https://nottingham-repository.worktribe.com/output/1394983
• Publisher URL: http://bio.biologists.org/content/7/10/bio037374