Golgi Oncoprotein <i>GOLPH3</i> Gene Expression Is Regulated by Functional E2F and CREB/ATF Promoter Elements

• Main Authors: Beatriz Peñalver-González, Jon Vallejo-Rodríguez, Gartze Mentxaka, Asier Fullaondo, Ainhoa Iglesias-Ara, Seth J. Field, Ana M. Zubiaga
• Format: Article
• Language: English
• Published: MDPI AG 2019-03-01
• Series: Genes
• Subjects: cell cycle; E2F factors; Golgi; <i>GOLPH3</i>; CREB/ATF; gene regulation
• Online Access: https://www.mdpi.com/2073-4425/10/3/247

The Golgi organelle duplicates its protein and lipid content to segregate evenly between two daughter cells after mitosis. However, how Golgi biogenesis is regulated during interphase remains largely unknown. Here we show that messenger RNA (mRNA) expression of <i>GOLPH3</i> and <i>GOLGA2</i>, two genes encoding Golgi proteins, is induced specifically in G1 phase, suggesting a link between cell cycle regulation and Golgi growth. We have examined the role of E2F transcription factors, critical regulators of G1 to S progression of the cell cycle, in the expression of Golgi proteins during interphase. We show that promoter activity for <i>GOLPH3</i>, a Golgi protein that is also oncogenic, is induced by E2F1-3 and repressed by E2F7. Mutation of the E2F motifs present in the <i>GOLPH3</i> promoter region abrogates E2F1-mediated induction of a <i>GOLPH3</i> luciferase reporter construct. Furthermore, we identify a critical CREB/ATF element in the <i>GOLPH3</i> promoter that is required for its steady state and ATF2-induced expression. Interestingly, depletion of <i>GOLPH3</i> with small interfering RNA (siRNA) delays the G1 to S transition in synchronized U2OS cells. Taken together, our results reveal a link between cell cycle regulation and Golgi function, and suggest that E2F-mediated regulation of Golgi genes is required for the timely progression of the cell cycle.