期刊
BIOLOGY OPEN
卷 7, 期 10, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/bio.037374
关键词
Survivin; Birc5; Autophagy; Lysosome; LC3
类别
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.
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