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Cells 2018, 7(10), 151; https://doi.org/10.3390/cells7100151

Drosophila HUWE1 Ubiquitin Ligase Regulates Endoreplication and Antagonizes JNK Signaling During Salivary Gland Development

1
Rappaport Research Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel
2
Institute of Pathology, RAMBAM Medical Center, Haifa 30196, Israel
3
Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel
4
Genome-Scale Biology Research Program Institute of Biomedicine University of Helsinki, 00290 Helsinki, Finland
5
Theodor Boveri Institute, Biocenter, University of Würzburg, D-97074 Würzburg, Germany
*
Author to whom correspondence should be addressed.
Received: 8 August 2018 / Revised: 20 September 2018 / Accepted: 21 September 2018 / Published: 26 September 2018
(This article belongs to the Special Issue Ubiquitination in Health and Disease)
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Abstract

The HECT-type ubiquitin ligase HECT, UBA and WWE Domain Containing 1, (HUWE1) regulates key cancer-related pathways, including the Myc oncogene. It affects cell proliferation, stress and immune signaling, mitochondria homeostasis, and cell death. HUWE1 is evolutionarily conserved from Caenorhabditis elegance to Drosophila melanogaster and Humans. Here, we report that the Drosophila ortholog, dHUWE1 (CG8184), is an essential gene whose loss results in embryonic lethality and whose tissue-specific disruption establishes its regulatory role in larval salivary gland development. dHUWE1 is essential for endoreplication of salivary gland cells and its knockdown results in the inability of these cells to replicate DNA. Remarkably, dHUWE1 is a survival factor that prevents premature activation of JNK signaling, thus preventing the disintegration of the salivary gland, which occurs physiologically during pupal stages. This function of dHUWE1 is general, as its inhibitory effect is observed also during eye development and at the organismal level. Epistatic studies revealed that the loss of dHUWE1 is compensated by dMyc proeitn expression or the loss of dmP53. dHUWE1 is therefore a conserved survival factor that regulates organ formation during Drosophila development. View Full-Text
Keywords: HECT; HUWE1; ubiquitin; salivary gland; endoreplication; JNK; dMyc; dmP53 HECT; HUWE1; ubiquitin; salivary gland; endoreplication; JNK; dMyc; dmP53
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Yanku, Y.; Bitman-Lotan, E.; Zohar, Y.; Kurant, E.; Zilke, N.; Eilers, M.; Orian, A. Drosophila HUWE1 Ubiquitin Ligase Regulates Endoreplication and Antagonizes JNK Signaling During Salivary Gland Development. Cells 2018, 7, 151.

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