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Published on: May 10, 2022
A novel ING2 isoform, ING2b, synergizes with ING2a to prevent cell cycle arrest and apoptosis
Motoko Unoki1, Kensuke Kumamoto, Ana I Robles
1Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, 37 Convent Dr., Bldg. 37, Rm. 3068, Bethesda, MD 20892, USA.
Abstract:
We identified a novel inhibitor of growth family member 2 (ING2) isoform, ING2b, which shares exon 2 with ING2a, but lacks the N-terminal p53 binding region. Contrary to ING2a, ING2b's promoter has no p53 binding sites. Consistently, activation of p53 led to suppression of ING2a, leaving ING2b unaffected. Through isoform-specific targeting, we showed that ING2a knockdown suppressed cell growth only in the presence of p53, ING2b knockdown had no effect on cell growth, and knockdown of both induced cell cycle arrest and apoptosis independently of p53. ING2a and ING2b have compensatory roles that protect cells from cell cycle arrest and apoptosis and may be involved in development of chemotherapeutic resistance.
Insights
Researchers discovered a new ING2b protein isoform that, along with ING2a, prevents cell cycle arrest and apoptosis. These ING2 isoforms may play a role in chemoresistance, offering new therapeutic targets.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The inhibitor of growth family member 2 (ING2) gene encodes multiple isoforms.
- ING2a and ING2b are known isoforms with distinct functional properties.
- The role of ING2 isoforms in cell cycle regulation and response to p53 is not fully understood.
Purpose of the Study:
- To identify and characterize a novel ING2 isoform, ING2b.
- To investigate the distinct roles of ING2a and ING2b in cell growth, cell cycle control, and apoptosis.
- To elucidate the relationship between ING2 isoforms, p53, and potential chemotherapeutic resistance.
Main Methods:
- Isoform-specific RNA interference (knockdown) was employed to target ING2a and ING2b.
- Cell growth, cell cycle progression, and apoptosis assays were performed.
- Analysis of p53 binding sites in the ING2 promoter regions was conducted.
Main Results:
- A novel ING2 isoform, ING2b, was identified, lacking the p53 binding domain present in ING2a.
- ING2a expression was suppressed by p53 activation, while ING2b remained unaffected.
- ING2a knockdown inhibited cell growth only in the presence of p53.
- Knockdown of both ING2a and ING2b induced cell cycle arrest and apoptosis independently of p53.
Conclusions:
- ING2a and ING2b exhibit compensatory roles in preventing cell cycle arrest and apoptosis.
- These ING2 isoforms may contribute to the development of chemotherapeutic resistance.
- Targeting ING2 isoforms presents a potential strategy for cancer therapy.
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