Aurora-A Interacts with AP-2α and Down Regulates Its Transcription Activity

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Aug 11

PMID 21829699

Citations 3

Authors

Lihui Zou

Yimin Sun

Mingrong Wang

Qimin Zhan

Affiliations

Soon will be listed here.

Abstract

Aurora-A is a serine/threonine protein kinase and plays an important role in the control of mitotic progression. Dysregulated expression of Aurora-A impairs centrosome separation and maturation, which lead to disrupted cell cycle progression and tumorigenesis. However, the molecular mechanism by which Aurora-A causes cell malignant transformation remains to be further defined. In this report, using transcription factors array and mRNA expression profiling array, we found that overexpression of Aurora-A suppressed transcription activity of AP-2α, a tumor suppressor that is often downregulated in variety of tumors, and inhibited expression of AP-2α-regulated downstream genes. These array-based observations were further confirmed by microwell colorimetric TF assay and luciferase reporter assay. Downregulated transcription activity of AP-2α by Aurora-A was found to be associated with reduced AP-2α protein stability, which appeared to be mediated by Aurora-A enhanced ubiquitin-dependent proteasomal degradation of AP-2α protein. Interestingly, Aurora-A-mediated AP-2α degradation was likely dependent Aurora-A kinase activity since inhibition of Aurora-A kinase activity was able to rescue Aurora-A-induced degradation of AP-2α. Moreover, we defined a physical interaction between Aurora-A and AP-2α, and such interaction might bridge the suppressive effect of Aurora-A on AP-2α protein stability. These findings provide new insights into molecular mechanism by which Aurora-A acts as an oncogenic molecule in tumor occurrence and malignant development.

Citing Articles

Crucial role of the transcription factors family activator protein 2 in cancer: current clue and views.

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Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma.

Shi K, Zhang J, Yang L, Li N, Yue Y, Du X BMC Cancer. 2021; 21(1):1196.

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Aurora A kinase (AURKA) in normal and pathological cell division.

Nikonova A, Astsaturov I, Serebriiskii I, Dunbrack Jr R, Golemis E Cell Mol Life Sci. 2012; 70(4):661-87.

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