FEBS Letters最新文献

Retraction: A. Mora, K. Sakamoto, E. J. McManus, and D. R. Alessi, "Role of the PDK1-PKB-GSK3 Pathway in Regulating Glycogen Synthase and Glucose Uptake in the Heart," FEBS Letters 579, no. 17 (2005): 3632-3638, https://doi.org/10.1016/j.febslet.2005.05.040. The above article, published online on 06 June 2005 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Michael Brunner; FEBS Press; and John Wiley and Sons Ltd. The journal was contacted by a representative of the research integrity group at the authors' institute, since an institutional investigation revealed inappropriate splicing and duplication of image sections within Fig. 2A, B and Fig. 3A. Consequently, the conclusions of the paper are substantially compromised, and the institute has recommended the paper to be retracted. The editors of the journal agree with the retraction based on the institutional investigation.

Psilocybin, the natural hallucinogen from Psilocybe (magic) mushrooms, is a highly promising drug candidate for the treatment of depression and several other mental health conditions. Biosynthesis of psilocybin from the amino acid l-tryptophan involves four strictly sequential modifications. The third of these, ATP-dependent phosphorylation of the intermediate 4-hydroxytryptamine, is catalysed by PsiK. Here we present a crystallographic analysis and a structure-based mutagenesis study of this kinase, providing insight into its mode of substrate recognition. The results of our work will support future bioengineering efforts aimed at generating variants of psilocybin with enhanced therapeutic properties.

The interaction of sclerostin (Scl) with the low-density lipoprotein receptor-related protein 4 (LRP4) leads to a marked reduction in bone formation by inhibiting the Wnt/β-catenin pathway. To characterize the Scl-LRP4 binding interface, we sorted a combinatorial library of Scl variants and isolated variants with reduced affinity to LRP4. We identified Scl single-mutation variants enriched during the sorting process and verified their reduction in affinity toward LRP4-a reduction that was not a result of changes in the variants' secondary structure or stability. We found that Scl positions K75 (loop 1) and V136 (loop 3) are critical hotspots for binding to LRP4. Our findings establish the foundation for targeting these hotspots for developing novel therapeutic strategies to promote bone formation.

Lambda interferons (IFNLs) provide critical host defense against pathogens encountered at mucosal surfaces. In humans, IFNL signaling is regulated in part by low and cell-type restricted expression of the lambda interferon receptor 1 protein with expression restricted primarily to epithelial cells located at mucosal surfaces. This review will examine the evidence suggesting a role for IFNLR1 transcriptional variants in mediating cell responsiveness to IFNL ligand exposure and regulation of pathway activity.

The protein folding problem was, to paraphrase Churchill, 'A riddle wrapped in a mystery inside an enigma'. The riddle, in this context, was the folding code; what interactions at the amino acid level are driving the folding process? The mystery was the kinetic question (Levinthal's paradox); how does the folding process occur so quickly (typically in timescales ranging from μS to mS)? Finally, the enigma represents the computational problem of developing approaches to predict the final folded sate of a protein given only its amino acid sequence. Herein, I trace the path to solving this riddle wrapped in a mystery inside an enigma.

Most tumors are resistant to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors, which may be due to impaired antigen presentation resulting from the downregulation of major histocompatibility complex class I (MHC-I) expression on tumor cells. We observed that platycodin D (PD), polygalacin D, and platycodin D2, which are plant-derived triterpenoid saponins, significantly reduced PD-L1 levels. RNA sequencing and the PharmMapper database analysis identified liver X receptor β (LXR-β) as a potential PD target. Further studies showed that PD reduces PD-L1 levels by binding to LXR-β and inhibiting LXR-β activity. Coadministration of PD and nintedanib, known to upregulate MHC-I expression, enhanced tumor recognition and killing by T cells. This study provides new insights into PD applications and mechanisms.

The primary cilium, a non-motile organelle present in most human cells, plays a crucial role in detecting microenvironmental changes and regulating intracellular signaling. Its dysfunction is linked to various diseases, including cancer. We explored the role of ciliated cells in prostate cancer by using Gefitinib and Jasplakinolide compounds to induce ciliated cells in both normal and tumor-like prostate cell lines. We assessed GLI1 and IFT20 expression and investigated YAP1 protein's role, which is implicated in primary cilium regulation. Finally, we examined these compounds in 3D cell models, aiming to simulate in vivo conditions. Our study highlights YAP1 as a potential target for novel genetic models to understand the primary cilium's role in mediating resistance to anticancer treatments.

Retinoic acid is crucial for vertebrate embryogenesis, influencing anterior-posterior patterning and organogenesis through its interaction with nuclear hormone receptors comprising heterodimers of retinoic acid receptors (RARα, β, or γ) and retinoid X receptors (RXRα, β, or γ). Tissue retinoic acid levels are tightly regulated since both its excess and deficiency are deleterious. Dehydrogenase/reductase 3 (DHRS3) plays a critical role in this regulation by converting retinaldehyde to retinol, preventing excessive retinoic acid formation. Mutations in DHRS3 can result in embryonic lethality and congenital defects. This study shows that mouse Dhrs3 expression is responsive to vitamin A status and is directly regulated by the RAR/RXR complex through cis-regulatory elements. This highlights a negative feedback mechanism that ensures retinoic acid homeostasis.

Autophagy, a highly conserved form of cellular recycling, is essential for cellular homeostasis. Its dysregulation has been linked to neurodegenerative diseases and various cancers, including breast cancer. We set out to determine if the RNA-binding protein (RBP) YBX3 regulates autophagy mRNAs, as previous findings suggest YBX3 depletion reduces distinct autophagy transcripts. We found that YBX3 interacts with and stabilizes the mRNA of the autophagy initiation factor ATG13 in HeLa, which in turn increases ATG13 protein expression. We have shown that this requires the 3' untranslated region (UTR) of ATG13 and occurs in other human cell lines, including HEK293, HepG2, and HCT116. Together, our data suggest a novel regulatory role for YBX3 of autophagy initiation through posttranscriptional control of ATG13 mRNA stability.

Many academics often have to face the pressure to constantly publish or quietly perish. The Publish or Perish Game™, a new tabletop game created by Max Bai, flips the script and offers a satirical reflection on the academic publishing process, turning the often-stressful endeavor into an entertainment experience. In this interview, Max Bai discusses the inspiration behind the game, the creative processes, and the broader impact he hopes the game will have on the academic community.