https://transhumanist.ru/index.php?action=history&feed=atom&title=CUL3CUL3 - История изменений2026-04-21T02:14:25ZИстория изменений этой страницы в викиMediaWiki 1.43.6https://transhumanist.ru/index.php?title=CUL3&diff=6294&oldid=prevOdysseusBot: Новая страница: «Cullin-3 (CUL-3) [KIAA0617] ==Publications== {{medline-entry |title=KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and age...»2021-05-12T15:21:57Z<p>Новая страница: «Cullin-3 (CUL-3) [KIAA0617] ==Publications== {{medline-entry |title=<a href="/index.php?title=KLHL22&action=edit&redlink=1" class="new" title="KLHL22 (страница не существует)">KLHL22</a> activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and age...»</p>
<p><b>Новая страница</b></p><div>Cullin-3 (CUL-3) [KIAA0617]<br />
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==Publications==<br />
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{{medline-entry<br />
|title=[[KLHL22]] activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and ageing.<br />
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29769719<br />
|abstract=The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that responds to a diverse set of environmental cues, including amino acids . Deregulation of mTORC1 has been linked with metabolic diseases, cancer and ageing . In response to amino acids, mTORC1 is recruited by the Rag GTPases to the lysosome, its site of activation . The GATOR1 complex, consisting of [[DEPDC5]], [[NPRL3]] and [[NPRL2]], displays GAP activity to inactivate Rag GTPases under amino-acid-deficient conditions . However, it is unclear how the inhibitory function of GATOR1 is released upon amino acid stimulation. Here we find that in response to amino acids, the [[CUL3]]-[[KLHL22]] E3 ubiquitin ligase promotes K48-linked polyubiquitination and degradation of [[DEPDC5]], an essential subunit of GATOR1. [[KLHL22]] plays a conserved role to mediate the activation of mTORC1 and downstream events in mammals and nematodes. Depletion of MEL-26, the Caenorhabditis elegans orthologue of [[KLHL22]], extends worm lifespan. Moreover, [[KLHL22]] levels are elevated in tumours of breast cancer patients, whereas [[DEPDC5]] levels are correspondingly reduced. Depletion of [[KLHL22]] in breast cancer cells suppresses tumour growth in nude mice. Therefore, pharmacological interventions targeting [[KLHL22]] may have therapeutic potential for the treatment of breast cancer and age-related diseases.<br />
|mesh-terms=* Adaptor Proteins, Signal Transducing<br />
* Aging<br />
* Animals<br />
* Autophagy<br />
* Breast Neoplasms<br />
* Caenorhabditis elegans<br />
* Caenorhabditis elegans Proteins<br />
* Carcinogenesis<br />
* Cell Line<br />
* Cell Proliferation<br />
* Cullin Proteins<br />
* Female<br />
* GTPase-Activating Proteins<br />
* Humans<br />
* Longevity<br />
* Mechanistic Target of Rapamycin Complex 1<br />
* Mice<br />
* Mice, Nude<br />
* Multiprotein Complexes<br />
* Oncogenes<br />
* Proteolysis<br />
* Repressor Proteins<br />
* Signal Transduction<br />
* Tumor Suppressor Proteins<br />
* Ubiquitin-Protein Ligases<br />
* Ubiquitination<br />
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|full-text-url=https://sci-hub.do/10.1038/s41586-018-0128-9<br />
}}</div>OdysseusBot