Yanku Yifat, Bitman-Lotan Eliya, Zohar Yaniv, Kurant Estee, Zilke Norman, Eilers Martin, Orian Amir
Rappaport Research Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
Institute of Pathology, RAMBAM Medical Center, Haifa 30196, Israel.
Cells. 2018 Sep 26;7(10):151. doi: 10.3390/cells7100151.
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 to and Humans. Here, we report that the ortholog, d (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 is compensated by dMyc proeitn expression or the loss of dmP53. dHUWE1 is therefore a conserved survival factor that regulates organ formation during development.
含HECT、UBA和WWE结构域的泛素连接酶1（HUWE1）调控包括Myc癌基因在内的关键癌症相关通路。它影响细胞增殖、应激和免疫信号传导、线粒体稳态以及细胞死亡。HUWE1在从果蝇到人类的进化过程中高度保守。在此，我们报告果蝇直系同源基因dHUWE1（CG8184）是一个必需基因，其缺失会导致胚胎致死，其组织特异性破坏确定了它在幼虫唾液腺发育中的调控作用。dHUWE1对唾液腺细胞的核内复制至关重要，其敲低导致这些细胞无法复制DNA。值得注意的是，dHUWE1是一种存活因子，可防止JNK信号过早激活，从而防止唾液腺在蛹期生理性解体。dHUWE1的这一功能具有普遍性，因为在眼睛发育和个体水平上也观察到了其抑制作用。上位性研究表明，dHUWE1的缺失可由dMyc蛋白表达或dmP53的缺失来补偿。因此，dHUWE1是一种保守的存活因子，在果蝇发育过程中调节器官形成。
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