A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit <a rel="external noopener" href="https://www.biorxiv.org/content/biorxiv/early/2019/08/30/750976.full.pdf">the original URL</a>. The file type is <code>application/pdf</code>.
TRIM21 and PHLDA3 Negatively Regulate the Cross-Talk between the PI3K/AKT Pathway and PPP Metabolism
[article]
<span title="2019-08-30">2019</span>
<i title="Cold Spring Harbor Laboratory">
bioRxiv
</i>
<span class="release-stage" >pre-print</span>
Preserved Fulltext
PI3K/AKT signaling is known to regulate cancer metabolism but whether metabolic pathway feedbacks and regulates the PI3K/AKT pathway is unclear. Here, we demonstrate the important reciprocal cross-talks between the PI3K/AKT signal and PPP branching metabolic pathways. PI3K/AKT activation stabilizes G6PD, the rate-limiting enzyme of PPP, by inhibiting a newly identified E3 ligase TIRM21, and promotes PPP. PPP metabolites, in turn, reinforce AKT activation and further promote cancer metabolic
<span class="external-identifiers">
<a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/750976">doi:10.1101/750976</a>
<a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/47i6qq63a5cwndzdxqdvotxdhm">fatcat:47i6qq63a5cwndzdxqdvotxdhm</a>
</span>
more »
... ogramming by blocking the expression of an AKT inhibitor PHLDA3. Knockout TRIM21 or PHLDA3 promotes the cross-talks and cell proliferation. Importantly, PTEN null human cancer cells and in vivo murine models are sensitive to anti-PPP treatments, suggesting the importance of PPP in maintaining AKT activation even in the presence of a constitutively activated PI3K pathway. Our study suggests that blockade of these reciprocal cross-talks may have a therapeutic benefit for cancers with PTEN loss or PI3K/AKT activation.
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20200324185120/https://www.biorxiv.org/content/biorxiv/early/2019/08/30/750976.full.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext">
<button class="ui simple right pointing dropdown compact black labeled icon button serp-button">
<i class="icon ia-icon"></i>
Web Archive
[PDF]
<div class="menu fulltext-thumbnail">
<img src="https://blobs.fatcat.wiki/thumbnail/pdf/7a/21/7a21e7758457af4329024295a2dc17603ef32b85.180px.jpg" alt="fulltext thumbnail" loading="lazy">
</div>
</button>
</a>
<a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/750976">
<button class="ui left aligned compact blue labeled icon button serp-button">
<i class="external alternate icon"></i>
biorxiv.org
</button>
</a>