Biology subjects

Patthy, L.

Publications and source records attributed to Patthy, L..

3 recordsLinked to original sources

bioRxiv2026

Lipid moieties of sonic hedgehog are important for interaction with its inhibitor, WIF1

It has been recognized a long time ago that the hedgehog (Hh) and Wnt signaling pathways have numerous similarities that suggest their common evolutionary origin. Although the Hh and Wnt proteins are unrelated they are similar in as much as they carry lipid modifications that are critical for their interaction with their receptors. In our earlier work we have shown that Wnt inhibitory factor 1 (WIF1), originally identified as a Wnt antagonist also binds to and inhibits the signaling activity of sonic hedgehog (Shh), raising the possibility that the lipid moieties of these unrelated morphogens play a dominant role in their interaction with WIF1. In the present work we have compared the interactions of human WIF1 protein with lipidated and non-lipidated forms of human sonic hedgehog (Shh) using Surface Plasmon Resonance spectroscopy and reporter assays monitoring the signaling activity of human Shh. Our studies have shown that human WIF1 protein has significantly higher affinity for lipidated than non-lipidated Shh, indicating that lipid modifications of Hhs are important for interactions with WIF1.

biochemistry↗

bioRxiv2025

Codon bias coevolves with longevity

Somatic mutations drive carcinogenesis and aging, shortening the lifespan of animals. Since the vulnerability of genes strongly depends on their size and the abundance of mutation hotspots, we have tested whether negative selection of hypermutable (e.g., CpG bearing) codons could play a role in the evolution of longevity in mammals. Our studies have shown that the CGA codon was significantly more depleted in long-lived than short-lived mammals, suggesting negative selection of this hypermutable stopogenic codon. Interestingly, our analyses have revealed lifespan-dependent changes in codon usage of most amino acids. In the case of a few amino acids (e.g., Ile) the change in codon usage favored translationally optimal codons in long-lived animals, reducing the chances of mistranslation and the formation of abnormal proteins. In the case of a larger group of amino acids (e.g., Tyr, Phe, Asp, Asn), however, the change in codon usage in long-lived animals favored translationally nonoptimal codons that lack matching isodecoder tRNAs. The most likely explanation for this observation is that slowdown of translation at these codons facilitates co-translational folding, thereby reducing the chances of misfolding and aggregation of misfolded proteins in long-lived animals. Our results suggest that the changes in codon usage may contribute significantly to correct co-translational folding, resulting in a more balanced proteostasis and a lower rate of cellular aging in long-lived animals. Our finding is in harmony with the notion that one of the most important hallmarks of aging is loss of proteostasis, manifested in the accumulation of abnormal, misfolded proteins.

evolutionary biology↗

bioRxiv2020

Use of signals of positive and negative selection to distinguish cancer genes and passenger genes

A major goal of cancer genomics is to identify all genes that play critical roles in carcinogenesis. Most approaches focused on genes that are positively selected for mutations that drive carcinogenesis and neglected the role of negative selection. Some studies have actually concluded that negative selection has no role in cancer evolution. In the present work we have re-examined the role of negative selection in tumor evolution through the analysis of the patterns of somatic mutations affecting the coding sequences of human genes. Our analyses have confirmed that tumor suppressor genes are positively selected for inactivating mutations. Oncogenes, however, were found to display signals of both negative selection for inactivating mutations and positive selection for activating mutations. Significantly, we have identified numerous human genes that show signs of strong negative selection during tumor evolution, suggesting that their functional integrity is essential for the growth and survival of tumor cells.

cancer biology↗