H3 clipping activity of glutamate dehydrogenase is regulated by stefin B and chromatin structure.
FEBS J
; 281(23): 5292-308, 2014 Dec.
Article
in En
| MEDLINE
| ID: mdl-25263734
ABSTRACT
Glutamate dehydrogenase has been recently identified as a tissue-specific histone H3-specific clipping enzyme. We have previously shown that it cleaves free as well as chromatin-bound histone H3. However, the physiological significance of this enzyme is still not clear. The present study aimed to improve our understanding of its significance in vivo. Using biochemical and cell biological approaches, we show that glutamate dehydrogenase is primarily associated with euchromatin, and it re-localizes from the nuclear periphery to the nucleolus upon DNA damage. The cysteine protease inhibitor stefin B regulates the H3 clipping activity of the enzyme. Chromatin structure and certain histone modifications influence H3 clipping activity. Interestingly, we also observed that an in vivo truncated form of H3 lacks H3K56 acetylation, which is a code for the DNA damage response. Together, these results suggest that glutamate dehydrogenase is a euchromatin-associated enzyme, and its H3 clipping activity is regulated by chromatin structure, histone modifications and an in vivo inhibitor. In response to DNA damage, it re-localizes to the nuclei, and hence may be involved in regulation of gene expression in vivo.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromatin
/
Histones
/
Cystatin B
/
Glutamate Dehydrogenase
Limits:
Animals
/
Humans
Language:
En
Journal:
FEBS J
Journal subject:
BIOQUIMICA
Year:
2014
Type:
Article
Affiliation country:
India