当前位置： SCI文献检索 > JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH期刊下所有文献 > Nuclear accumulation of UBC9 contributes to SUMOylation of lamin A/C and nucleophagy in response to DNA damage.

Nuclear accumulation of UBC9 contributes to SUMOylation of lamin A/C and nucleophagy in response to DNA damage.

Abstract：

BACKGROUND:Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved intracellular mechanism for lysosomal degradation of damaged cellular components. The specific degradation of nuclear components by the autophagy pathway is called nucleophagy. Most studies have focused on autophagic turnover of cytoplasmic materials, and little is known about the role of autophagy in the degradation of nuclear components. METHODS:Human MDA-MB-231 and MCF-7 breast cancer cell lines were used as model systems in vitro. Induction of nucleophagy by nuclear DNA leakage was determined by western blot and immunofluorescence analyses. The interaction and colocalization of LC3 and lamin A/C was determined by immunoprecipitation and immunofluorescence. The role of the SUMO E2 ligase, UBC9, on the regulation of SUMOylation of lamin A/C and nucleophagy was determined by siRNA silencing of UBC9, and analyzed by immunoprecipitation and immunofluorescence. RESULTS:DNA damage induced nuclear accumulation of UBC9 ligase which resulted in SUMOylation of lamin A/C and that SUMOylation of this protein was required for the interaction between the autophagy protein LC3 and lamin A/C, which was required for nucleophagy. Knockdown of UBC9 prevented SUMOylation of lamin A/C and LC3-lamin A/C interaction. This attenuated nucleophagy which degraded nuclear components lamin A/C and leaked nuclear DNA mediated by DNA damage. CONCLUSIONS:Our findings suggest that nuclear DNA leakage activates nucleophagy through UBC9-mediated SUMOylation of lamin A/C, leading to degradation of nuclear components including lamin A/C and leaked nuclear DNA.

journal_name

J Exp Clin Cancer Res

journal_title

Journal of experimental & clinical cancer research : CR

authors

Li Y,Jiang X,Zhang Y,Gao Z,Liu Y,Hu J,Hu X,Li L,Shi J,Gao N

doi

10.1186/s13046-019-1048-8

subject

Has Abstract

pub_date

2019-02-11 00:00:00

pages

67

issue

1

eissn

0392-9078

issn

1756-9966

pii

10.1186/s13046-019-1048-8

journal_volume

38

pub_type

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