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AP2 inhibits cancer cell growth and activates p21WAF1/CIP1 expression

Nature Genetics volume 15, pages 78–82 (1997)Cite this article

Abstract

The 52-kD Activator Protein (AP2) is a DMA-binding transcription factor1–3 implicated in signalling terminal differentiation2–4. Profound developmental abnormalities have been recently observed in AP2-null mice5,6. The molecular events by which AP2 promotes differentiation or development are, however, unknown. Increased expression of the universal cell cycle inhibitor P21WAF1/CIP1 occurs in growth-arrested terminally differentiating cells7–12. In a search for cellular factors that could activate p21 during phorbol ester (TPA)-induced differentiation, we identified AP2 as a regulator of p21 expression. Mutagenesis of an AP2 DMA-binding site within a p21 promoter-luciferase reporter inhibited its activation by either AP2 transfection or TPA stimulation. Endogenous p21 protein levels were elevated and DMA synthesis was inhibited in AP2 versus control vector-transfected cells. Overexpression of AP2 in HepG2 human hepatoblastoma and SW480 human colon adenocarcinoma cells inhibited cell division and stable colony formation. These results link the differentiation-associated factor AP2 to negative cell cycle and growth control, possibly through p21 activation.

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Author notes

  1. Wafik S. El-Deiry: All correspondence should be addressed to W.S.E.-D.

Authors and Affiliations

  1. Howard Hughes Medical Institute, Laboratory of Molecular Oncology and Cell Cycle Regulation, Department of Medicine and Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA

    Yi-Xin Zeng, Kumaravel Somasundaram & Wafik S. El-Deiry

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  1. Yi-Xin Zeng
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  2. Kumaravel Somasundaram
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  3. Wafik S. El-Deiry
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Zeng, YX., Somasundaram, K. & El-Deiry, W. AP2 inhibits cancer cell growth and activates p21WAF1/CIP1 expression. Nat Genet 15, 78–82 (1997). https://doi.org/10.1038/ng0197-78

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