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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
p53 acts as a co-repressor to regulate keratin 14 expression during epidermal cell differentiation
Bi-He Cai1, Pei-Ching Hsu, I-Lun Hsin
1Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Plos One
|August 23, 2012
Summary
p53 acts as a co-repressor, binding to SP1 to down-regulate keratin 14 (K14) expression during epidermal cell differentiation. This interaction is enhanced by TPA-induced p53 phosphorylation.
Area of Science:
- Cell biology
- Molecular biology
- Dermatology
Background:
- Keratin 14 (K14) expression decreases during epidermal differentiation.
- p53 activity and its target genes (p21, 14-3-3σ) increase during this process.
- The precise mechanism linking p53 and K14 regulation was unclear.
Purpose of the Study:
- To investigate the regulatory relationship between p53 and keratin 14 (K14) expression.
- To elucidate the role of p53 in down-regulating K14 during epidermal differentiation.
Main Methods:
- Constructed various K14 promoter variants to assess p53's effect.
- Utilized DNA affinity precipitation assays to detect protein-DNA interactions.
- Employed a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced differentiation model in cell lines (H1299, C9) and primary keratinocytes (PHFK).
- Assessed the impact of p53 inhibition (dominant-negative mutant ΔTAp53, pifithrin-α) on K14 expression.
Main Results:
- Wild-type p53 repressed K14 promoter activity.
- A mutation in the SP1 binding site abolished p53-mediated repression of K14.
- p53 was confirmed to form a complex with SP1 at the K14 promoter's SP1 binding site.
- TPA-induced differentiation led to K14 down-regulation, which was prevented by inhibiting p53 activity.
- TPA treatment induced p53 phosphorylation at residue 378, enhancing its binding to SP1 and K14 repression.
Conclusions:
- p53 acts as a co-repressor, down-regulating K14 expression by binding to SP1.
- p53-mediated repression of K14 is a key event in TPA-induced epidermal differentiation.
- Phosphorylation of p53 enhances its ability to repress K14 expression during differentiation.
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