Interaction of Sp1 and APP promoter elucidates a mechanism for Pb²⁺ caused neurodegeneration

Qi GAO, Ziwen DAI, Shiqing ZHANG, Yuqiang FANG, Kin Lam Ken YUNG, Pik Kwan LO, King Wai Chiu LAI

Research output: Contribution to journalArticlespeer-review

5 Citations (Scopus)


A ubiquitously expressed transcription factor, specificity protein 1 (Sp1), interacts with the amyloid precursor protein (APP) promoter and likely mediates APP expression. Promoter-interaction strengths variably regulate the level of APP expression. Here, we examined the interactions of finger 3 of Sp1 (Sp1–f3) with a DNA fragment containing the APP promoter in different ionic solutions using atomic force microscope (AFM) spectroscopy. Sp1–f3 molecules immobilized on an Si substrate were bound to the APP promoter, which was linked to the AFM tips via covalent bonds. The interactions were strongly influenced by Pb2+, considering that substituting Zn2+ with Pb2+ increased the binding affinity of Sp1 for the APP promoter. The results revealed that the enhanced interaction force facilitated APP expression and that APP overexpression could confer a high-risk for disease incidence. An increased interaction force between Sp1–f3 and the APP promoter in Pb2+ solutions was consistent with a lower binding free energy, as determined by computer-assisted analysis. The impact of Pb2+ on cell morphology and related mechanical properties were also detected by AFM. The overexpression of APP caused by the enhanced interaction force triggered actin reorganization and further resulted in an increased Young's modulus and viscosity. The correlation with single-force measurements revealed that altered cellular activities could result from alternation of Sp1–APP promoter interaction. Our AFM findings offer a new approach in understanding Pb2+ associated neurodegeneration. Copyright © 2020 Elsevier Inc. All rights reserved.

Original languageEnglish
Article number108265
JournalArchives of Biochemistry and Biophysics
Early online dateJan 2020
Publication statusPublished - Mar 2020


Gao, Q., Dai, Z., Zhang, S., Fang, Y., Yung, K. K. L., Lo, P. K., & Lai, K. W. C. (2020). Interaction of Sp1 and APP promoter elucidates a mechanism for Pb²⁺ caused neurodegeneration. Archives of Biochemistry and Biophysics, 681, Article 108265.


Dive into the research topics of 'Interaction of Sp1 and APP promoter elucidates a mechanism for Pb²⁺ caused neurodegeneration'. Together they form a unique fingerprint.