Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.6.3.1 (
NADPH oxidase
)
11,281
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
HIPK2
is a stress-induced kinase and a transcriptional corepressor that functionally cooperates with p53 to suppress cancer. Activation of the p53 proapoptotic function requires a cascade of phosphorylations and acetylations, and
HIPK2
takes part in both modifications in that it phosphorylates p53 Ser46 and induces p53 Lys382 acetylation. Here, to further investigate the role of
HIPK2
in p53 activation, we started with the finding that
HIPK2
inhibition upregulated Nox1, a homolog of the catalytic subunit of the superoxide-generating
NADPH oxidase
, involved in tumor progression and ROS production. We found that Nox1 inhibited p53 Lys382 acetylation, which is a target of SIRT1 deacetylase, and impaired p53 proapoptotic transcriptional activity. By the use of either small interfering RNAs to target SIRT1 or the SIRT1 inhibitor nicotinamide we found that Nox1-dependent inhibition of p53 transcriptional activity was SIRT1-dependent. Thus, Nox1 was unable to inhibit p53 when coexpressed with a SIRT1 deacetylase-defective mutant (SIRT1HY), suggesting a link between Nox1 and SIRT1 activity. Finally, recovery of
HIPK2
function downregulated Nox1 expression with rescue of p53 Lys382 acetylation and p53 activity. Together, our findings indicate that Nox1 upregulation may activate SIRT1 and inhibit p53 and that Lys382 is important for p53 proapoptotic function.
...
PMID:Nox1 is involved in p53 deacetylation and suppression of its transcriptional activity and apoptosis. 2017 Dec 73
