| RRC ID |
70758
|
| 著者 |
Chang YC, Peng YX, Yu BH, Chang HC, Liang PS, Huang TY, Shih CJ, Chu LA, Sang TK.
|
| タイトル |
VCP maintains nuclear size by regulating the DNA damage-associated MDC1-p53-autophagy axis in Drosophila.
|
| ジャーナル |
Nat Commun
|
| Abstract |
The maintenance of constant karyoplasmic ratios suggests that nuclear size has physiological significance. Nuclear size anomalies have been linked to malignant transformation, although the mechanism remains unclear. By expressing dominant-negative TER94 mutants in Drosophila photoreceptors, here we show disruption of VCP (valosin-containing protein, human TER94 ortholog), a ubiquitin-dependent segregase, causes progressive nuclear size increase. Loss of VCP function leads to accumulations of MDC1 (mediator of DNA damage checkpoint protein 1), connecting DNA damage or associated responses to enlarged nuclei. TER94 can interact with MDC1 and decreases MDC1 levels, suggesting that MDC1 is a VCP substrate. Our evidence indicates that MDC1 accumulation stabilizes p53A, leading to TER94K2A-associated nuclear size increase. Together with a previous report that p53A disrupts autophagic flux, we propose that the stabilization of p53A in TER94K2A-expressing cells likely hinders the removal of nuclear content, resulting in aberrant nuclear size increase.
|
| 巻・号 |
12(1)
|
| ページ |
4258
|
| 公開日 |
2021-7-12
|
| DOI |
10.1038/s41467-021-24556-0
|
| PII |
10.1038/s41467-021-24556-0
|
| PMID |
34253734
|
| PMC |
PMC8275807
|
| MeSH |
Animals
Autophagy*
Biomarkers / metabolism
Cell Nucleus / metabolism*
Cell Nucleus Size*
Compound Eye, Arthropod
DNA Damage*
DNA Repair
DNA-Binding Proteins / metabolism*
Drosophila Proteins / metabolism*
Drosophila melanogaster / metabolism*
Mitosis
Signal Transduction
Time Factors
Tumor Suppressor Protein p53 / metabolism*
Ubiquitinated Proteins / metabolism
Valosin Containing Protein / metabolism*
|
| IF |
12.121
|
| リソース情報 |
| ショウジョウバエ |
DGRC#111109 |
