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J. Dev. Biol. 2018, 6(1), 2; https://doi.org/10.3390/jdb6010002

The Biology of SUMO-Targeted Ubiquitin Ligases in Drosophila Development, Immunity, and Cancer

1
Genentech, 1 DNA Way, South San Francisco, CA 94080, USA
2
Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109610, Israel
*
Author to whom correspondence should be addressed.
Received: 28 November 2017 / Revised: 27 December 2017 / Accepted: 27 December 2017 / Published: 1 January 2018
(This article belongs to the Special Issue Drosophila - A Model System for Developmental Biology)
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Abstract

The ubiquitin and SUMO (small ubiquitin-like modifier) pathways modify proteins that in turn regulate diverse cellular processes, embryonic development, and adult tissue physiology. These pathways were originally discovered biochemically in vitro, leading to a long-standing challenge of elucidating both the molecular cross-talk between these pathways and their biological importance. Recent discoveries in Drosophila established that ubiquitin and SUMO pathways are interconnected via evolutionally conserved SUMO-targeted ubiquitin ligase (STUbL) proteins. STUbL are RING ubiquitin ligases that recognize SUMOylated substrates and catalyze their ubiquitination, and include Degringolade (Dgrn) in Drosophila and RNF4 and RNF111 in humans. STUbL are essential for early development of both the fly and mouse embryos. In the fly embryo, Dgrn regulates early cell cycle progression, sex determination, zygotic gene transcription, segmentation, and neurogenesis, among other processes. In the fly adult, Dgrn is required for systemic immune response to pathogens and intestinal stem cell regeneration upon infection. These functions of Dgrn are highly conserved in humans, where RNF4-dependent ubiquitination potentiates key oncoproteins, thereby accelerating tumorigenesis. Here, we review the lessons learned to date in Drosophila and highlight their relevance to cancer biology. View Full-Text
Keywords: ubiquitin; SUMO; Dgrn; SUMO-targeted ubiquitin ligases RNF4; transcription; gene regulation; development; immunity; cancer ubiquitin; SUMO; Dgrn; SUMO-targeted ubiquitin ligases RNF4; transcription; gene regulation; development; immunity; cancer
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Abed, M.; Bitman-Lotan, E.; Orian, A. The Biology of SUMO-Targeted Ubiquitin Ligases in Drosophila Development, Immunity, and Cancer. J. Dev. Biol. 2018, 6, 2.

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