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Here, we describe a novel, evolutionarily conserved feedback system operating at a sterol-specific step of the mevalonate pathway.
Decades of research have revealed that these different regulatory protein complexes interact in an elaborate, yet highly conserved feedback loop to establish and maintain epithelial polarity (Bilder et al., 2003; St Johnston and Ahringer, 2010; Laprise and Tepass, 2011; Rodriguez-Boulan and Macara, 2014).
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We demonstrate, that with respect to this model the amount of predicted conserved autoregulatory feedback loops is significantly higher than expected when conservation between human and chicken, danio or fugu is studied.
These findings reveal an evolutionarily conserved positive feedback mechanism underlying robustness of the Hippo pathway in size control and tumorigenesis.
In particular CK1 and CK2 have been shown to be part of conserved transcriptional/translational feedback loops in eukaryotes that regulate circadian clocks, based on pharmacological and overexpression results [ 28, 31, 32].
We propose that Yurt is part of an evolutionary conserved negative-feedback mechanism that restricts Crb complex activity in promoting apical membrane formation.
Summarizing, we have shown that the number of autoregulatory feedback loops conserved between human and fugu, danio or chicken is significantly higher than expected in the site- and gene-oriented models.
Several components of these feedback loops are conserved with mammals [1].
It has therefore been proposed that the FGF-Sprouty feedback loop is conserved between cnidarian and bilaterian animals [ 2].
When varying the input noise frequency (Supplementary Figure S6) or replacing the uniformly distributed noise by the white noise (Supplementary Figure S7), the relations among NAR, iSAT, and sensitivity are conserved in the single positive feedback module.
This observation may suggest that feedbacks can be conserved even when connections are rewired.
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