Caspase-mediated cleavage of C53/LZAP protein causes abnormal microtubule bundling and rupture of the nuclear envelope

Jianchun Wu, Hai Jiang, Shouqing Luo, Mingsheng Zhang, Yinghua Zhang, Fei Sun, Shuang Huang, Honglin Li

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Apoptotic nucleus undergoes distinct morphological and biochemical changes including nuclear shrinkage, chromatin condensation and DNA fragmentation, which are attributed to caspase-mediated cleavage of several nuclear substrates such as lamins. As most of active caspases reside in the cytoplasm, disruption of the nuclear-cytoplasmic barrier is essential for caspases to reach their nuclear targets. The prevailing proposed mechanism is that the increase in the permeability of nuclear pores induced by caspases allows the caspases and other apoptotic factors to diffuse into the nucleus, thereby resulting in the nuclear destruction. Here, we report a novel observation that physical rupture of the nuclear envelope (NE) occurs in the early stage of apoptosis. We found that the NE rupture was caused by caspase-mediated cleavage of C53/LZAP, a protein that has been implicated in various signaling pathways, including NF-κB signaling and DNA damage response, as well as tumorigenesis and metastasis. We also demonstrated that C53/LZAP bound indirectly to the microtubule (MT), and expression of the C53/LZAP cleavage product caused abnormal MT bundling and NE rupture. Taken together, our findings suggest a novel role of C53/LZAP in the regulation of MT dynamics and NE structure during apoptotic cell death. Our study may provide an additional mechanism for disruption of the nuclear-cytoplasmic barrier during apoptosis.

Original languageEnglish (US)
Pages (from-to)691-704
Number of pages14
JournalCell Research
Volume23
Issue number5
DOIs
StatePublished - May 2013

Keywords

  • C53/LZAP
  • apoptosis
  • caspase
  • microtubule
  • nuclear envelope

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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