Nonhistone human chromatin protein PC4 is critical for genomic integrity and negatively regulates autophagy.
AMPK pathway
autophagy inhibition
chromatin dynamics
gamma radiation resistance
histone acetylation
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
19
04
2019
revised:
13
05
2019
accepted:
04
06
2019
pubmed:
7
6
2019
medline:
17
6
2020
entrez:
7
6
2019
Statut:
ppublish
Résumé
Multifunctional human transcriptional positive co-activator 4 (PC4) is a bona fide nonhistone component of the chromatin and plays a pivotal role in the process of chromatin compaction and functional genome organization. Knockdown of PC4 expression causes a drastic decompaction which leads to open conformation of the chromatin, and thereby altered nuclear architecture, defects in chromosome segregation and changed epigenetic landscape. Interestingly, these defects do not induce cellular death but result in enhanced cellular proliferation, possibly through enhanced autophagic activity. Moreover, PC4 depletion confers significant resistance to gamma irradiation. Exposure to gamma irradiation further induced autophagy in these cells. Inhibition of autophagy by small molecule inhibitors as well as by silencing of a critical autophagy gene drastically reduces the ability of PC4 knockdown cells to survive. On the contrary, complementation with wild-type PC4 could reverse this phenomenon, confirming the process of autophagy as the key mechanism for radiation resistance in the absence of PC4. These data connect the unexplored role of chromatin architecture in regulating autophagy during stress conditions such as radiation.
Substances chimiques
Chromatin
0
DNA-Binding Proteins
0
SUB1 protein, human
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4422-4442Subventions
Organisme : Wellcome Trust/DBT India Alliance Intermediate Fellowship
ID : 500159/Z/09/Z
Pays : International
Organisme : JNCASR
Pays : International
Informations de copyright
© 2019 Federation of European Biochemical Societies.
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