Next Article in Journal
Emerging Picture of Deuterosome-Dependent Centriole Amplification in MCCs
Previous Article in Journal
Epigenetic Study in Parkinson’s Disease: A Pilot Analysis of DNA Methylation in Candidate Genes in Brain
Previous Article in Special Issue
Control of DNA Replication Initiation by Ubiquitin
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Cells 2018, 7(10), 151;

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

Rappaport Research Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel
Institute of Pathology, RAMBAM Medical Center, Haifa 30196, Israel
Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel
Genome-Scale Biology Research Program Institute of Biomedicine University of Helsinki, 00290 Helsinki, Finland
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)
Full-Text   |   PDF [4062 KB, uploaded 27 September 2018]   |  


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

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top