Headcase and Unkempt Regulate Tissue Growth and Cell Cycle Progression in Response to Nutrient Restriction
| Autor: | Yulan Xiong, Qinfang Liu, Jianzhong Yu, Naren Li |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell Cycle Cell cycle progression Nutrients mTORC1 Biology S6 phosphorylation Article General Biochemistry Genetics and Molecular Biology Cell biology law.invention 03 medical and health sciences Tumor suppressor proteins 030104 developmental biology 0302 clinical medicine law embryonic structures Disease Progression Animals Suppressor Drosophila 030217 neurology & neurosurgery Function (biology) Signal Transduction |
| Zdroj: | Cell reports |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2018.12.086 |
| Popis: | SUMMARY Nutrient restriction (NR) decreases the incidence and growth of many types of tumors, yet the underlying mechanisms are not fully understood. In this study, we identified Headcase (Hdc) and Unkempt (Unk) as two NR-specific tumor suppressor proteins that form a complex to restrict cell cycle progression and tissue growth in response to NR in Drosophila. Loss of Hdc or Unk does not confer apparent growth advantage under normal nutrient conditions but leads to accelerated cell cycle progression and tissue overgrowth under NR. Hdc and Unk bind to the TORC1 component Raptor and preferentially regulate S6 phosphorylation in a TORC1-dependent manner. We further show that HECA and UNK, the human counterparts of Drosophila Hdc and Unk, respectively, have a conserved function in regulating S6 phosphorylation and tissue growth. The identification of Hdc and Unk as two NR-specific tumor suppressors provides insight into molecular mechanisms underlying the anti-tumorigenic effects of NR. In Brief The molecular mechanisms underlying nutrient restriction resistance remain unclear. Li et al. find that Hdc and Unk function in the mTOR signaling pathway to restrict tissue growth and cell cycle progression in response to nutrient restriction. Graphical Abstract |
| Databáze: | OpenAIRE |
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