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Stat3 activation of NF-{kappa}B p100 processing involves CBP/p300-mediated acetylation.
Nagalakshmi Nadiminty1, Wei Lou, Soo Ok Lee
1Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Summary
Active Signal transducer and activator of transcription 3 (Stat3) promotes the conversion of NF-kappaB p100 to p52, a process critical for cancer cell survival and therapy escape. This pathway involves IKKalpha activation and acetylation by CBP/p300.
Area of Science:
- Molecular Biology
- Cancer Biology
- Signal Transduction
Background:
- The noncanonical NF-kappaB pathway regulates NF-kappaB p100 processing to p52, with dysregulation linked to lymphocyte hyperplasia and transformation.
- Active Signal transducer and activator of transcription 3 (Stat3) is prevalent in human cancers, promoting cell proliferation and survival.
Purpose of the Study:
- To investigate the role of active Stat3 in the proteolytic processing of NF-kappaB p100 to p52.
- To elucidate the molecular mechanisms underlying Stat3-mediated p100 to p52 conversion and its implications for cancer cell survival.
Main Methods:
- Investigated Stat3's effect on p100 processing in cancer cells.
- Utilized a mutant Stat3 defective in acetylation to assess its role in the pathway.
- Examined the impact of p52 overexpression on apoptotic cell death.
Main Results:
- Active Stat3 induces p100 processing to p52 via IKKalpha activation and p100 phosphorylation.
- Stat3-mediated p100 processing requires acetylation by CREB-binding protein (CBP)/p300.
- Overexpression of p52 confers protection against apoptotic cell death.
Conclusions:
- Stat3 activation of p100 to p52 processing is a key mechanism for cancer cell survival.
- This Stat3-driven pathway represents a common strategy for cancer cells to evade therapeutic interventions.