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Genes 2019, 10(3), 247; https://doi.org/10.3390/genes10030247

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

1
Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country UPV/EHU, 48080 Bilbao, Spain
2
Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA 92093, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 22 February 2019 / Revised: 12 March 2019 / Accepted: 20 March 2019 / Published: 25 March 2019
(This article belongs to the Special Issue Cell Cycle and Regulation)
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Abstract

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 GOLPH3 and GOLGA2, 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 GOLPH3, a Golgi protein that is also oncogenic, is induced by E2F1-3 and repressed by E2F7. Mutation of the E2F motifs present in the GOLPH3 promoter region abrogates E2F1-mediated induction of a GOLPH3 luciferase reporter construct. Furthermore, we identify a critical CREB/ATF element in the GOLPH3 promoter that is required for its steady state and ATF2-induced expression. Interestingly, depletion of GOLPH3 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. View Full-Text
Keywords: cell cycle; E2F factors; Golgi; GOLPH3; CREB/ATF; gene regulation cell cycle; E2F factors; Golgi; GOLPH3; CREB/ATF; gene regulation
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Peñalver-González, B.; Vallejo-Rodríguez, J.; Mentxaka, G.; Fullaondo, A.; Iglesias-Ara, A.; Field, S.J.; Zubiaga, A.M. Golgi Oncoprotein GOLPH3 Gene Expression Is Regulated by Functional E2F and CREB/ATF Promoter Elements. Genes 2019, 10, 247.

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