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Citation
Yanku, Y., Bitman-Lotan, E., Zohar, Y., Kurant, E., Zilke, N., Eilers, M., Orian, A. (2018). Drosophila HUWE1 Ubiquitin Ligase Regulates Endoreplication and Antagonizes JNK Signaling During Salivary Gland Development.  Cells 7(10): E151.
FlyBase ID
FBrf0240182
Publication Type
Research paper
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 Drosophilamelanogaster 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.

PubMed ID
PubMed Central ID
PMC6210797 (PMC) (EuropePMC)
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    Language of Publication
    English
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    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cells
    Title
    Cells
    ISBN/ISSN
    2073-4409
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