FEBS Letters最新文献

Dipeptidyl peptidase IV (DPPIV) family proteases are classically defined by their strict removal of N-terminal dipeptides from substrates bearing a proline or alanine at the P₁ position. Here, we report that both Caenorhabditis elegans DPF-3 and human DPP4 (hDPP4) possess previously unrecognized tripeptidyl peptidase activity in addition to dipeptidyl peptidase activity. This activity plays a key role in the processing of the WAGO-1 protein N-terminus, which is essential for proper small-RNA loading, germline genome defense, and fertility. Kinetic analyses using the fluorogenic substrate H-Met-Gly-Pro-AMC further demonstrated that, in vitro, DPF-3 and hDPP4 can liberate AMC. These findings potentially expand the substrate repertoire of DPPIV proteases, suggesting that these proteases could function as versatile N-terminal processors, with important implications for nascent protein maturation.

The HtrA family of proteins is known for its dual role as chaperones and proteases. In Helicobacter pylori (H. pylori), HtrA's chaperone and proteolytic activities are crucial for the bacterium's survival and successful host infection. Compared to other HtrA homologs in Gram-negative bacteria, HtrA of H. pylori (HtrA_Hp) is rather well-understood. HtrA is localized in two cellular compartments, performing critical functions within the bacterial periplasm as well as in the extracellular milieu. This review aimed to summarize the current knowledge on HtrA_Hp and provide comprehensive information about (i) the structure, oligomerization, and general properties of HtrA_Hp, (ii) its chaperone and proteolytic activity in the stress response and the protein quality control system in the periplasm, and (iii) the functional role of HtrA_Hp in opening lateral cell junction complexes of epithelial cells as an important step in infectivity. Due to its essential physiological role and its contribution to the pathologic consequences of infection, HtrA represents a highly attractive target for novel therapeutic strategies.

Wound healing in the skin is a coordinated process in which the extracellular matrix (ECM) plays a central regulatory role. While the structural constituents of the ECM, such as collagens and elastin, are responsible for the shape and mechanical strength of the tissue, the modulatory functions of the ECM are largely mediated by nonstructural matricellular proteins. These proteins bind to structural ECM components, cell surface receptors and other extracellular molecules to fine-tune cellular behaviour throughout the different phases of wound healing. The signalling cascades evoked by matricellular proteins modulate key cellular processes, including proliferation, migration and differentiation-functions essential for effective tissue regeneration. This review provides an update about the mechanisms by which matricellular proteins orchestrate the wound healing process.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a multidomain enzyme essential for the DNA damage response; its inhibition can lead to cancer cell death. Recruitment of PARP-1 to sites of genomic damage is mediated by its zinc finger domains. In this study, we investigated the inhibition of PARP-1's DNA-dependent activation by three Au(I)-based drugs, presumable zinc-ejectors. We found that aurothioglucose and sodium aurothiomalate selectively inhibited PARP-1's DNA-dependent activity, with IC₅₀ values in the nanomolar range, while preserving its DNA-independent activity. Furthermore, in a BRCA-mutated cell line, both compounds effectively suppressed DNA replication, with half-maximal effective concentrations (EC₅₀) also in the nanomolar range. These findings highlight the potential of selective, zinc finger–targeting PARP-1 inhibitors as promising candidates for anticancer drug testing.

Expression of Concern: D.M. Price, C.L. Chik, D. Terriff, J. Weller, A. Humphries, D.A. Carter, D.C. Klein, and A.K. Ho, “Mitogen-Activated Protein Kinase Phosphatase-1 (MKP-1): >100-Fold Nocturnal and Norepinephrine-Induced Changes in the Rat Pineal Gland,” FEBS Letters 577, no. 1-2 (2004): 220-226, https://doi.org/10.1016/j.febslet.2004.09.083.

This Expression of Concern is for the above article, published online on 18 October 2004 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Michael Brunner; Federation of European Biochemical Societies (FEBS); and John Wiley & Sons Ltd. A third party alerted the journal to possible duplications of the GADPH loading control bands in Figures 1B, 2B, and 3B. The journal verified the duplications and the publisher attempted to contact the authors for original data and comments. The authors did not respond to the publisher's requests. In the absence of the original data, the journal and publisher are unable to fully investigate the identified duplications. Therefore, the journal has decided to issue an Expression of Concern to inform and alert readers.

RETRACTION: Y. Xu, J. He, Y. Wang, X. Zhu, Q. Pan, Q. Xie and F. Sun, “ miR-889 Promotes Proliferation of Esophageal Squamous Cell Carcinomas Through DAB2IP,” FEBS Letters 589, no. 10 (2015): 1127-1135, https://doi.org/10.1016/j.febslet.2015.03.027.

The above article, published online on 01 April 2015 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Michael Brunner; the Federation of European Biochemical Societies; and John Wiley & Sons Ltd. The retraction has been agreed upon following concerns raised by a third party. Following an investigation, duplicated elements were identified between Figures 2A and 5C, as well as between Figures 2B and 5C. Furthermore, inconsistencies were observed in the siDAB2IP colonies shown in Figures 4C and 4D. Finally, in Figure 6A, the 400x panel for Tumor #1 does not correspond to the 200x panel. The author cooperated with the investigation, stating that the duplications were an error due to figure mismanagement and provided some supporting data. However, the data provided was not considered to be satisfactory. Given the extent of the identified issues, the editors have lost confidence in the data presented and consider the conclusions to be compromised.

Phosphatidylinositol 4-kinases (PI4Ks) are pivotal enzymes responsible for the generation of phosphatidylinositol 4-phosphate (PI4P), a key precursor involved in various cellular signalling pathways that regulate vesicular trafficking, Golgi maintenance and intracellular communication. Conserved across eukaryotic species, PI4Ks exist in distinct isoforms with specific localisations and functions, ranging from plasma membrane dynamics to endosomal trafficking and autophagy regulation. Notably, numerous pathogens, including viruses, bacteria and parasites, have evolved mechanisms to hijack host PI4Ks, thereby facilitating intracellular replication and survival. For example, RNA viruses within the Flaviviridae and Coronaviridae families recruit PI4Ks to remodel host membranes for the assembly of replication complexes. Similarly, intracellular bacteria such as Salmonella and Legionella manipulate PI4P-enriched compartments to evade host defences and promote replication. Due to their central roles in both normal cellular physiology and infection, PI4Ks have emerged as promising therapeutic targets. A variety of inhibitors, including ATP-competitive compounds, have been developed and evaluated for their antiviral, antibacterial and antiparasitic potential. Nevertheless, challenges related to selectivity and toxicity remain. Recent advances include the identification of inhibitors effective against Plasmodium species and the development of compounds targeting PI4KIIIβ in infections with viruses such as hepatitis C and coronaviruses. This review highlights the dual role of PI4Ks as essential cellular regulators and exploitable pathogen cofactors, underscoring their potential as drug targets. Continued investigation into the structure, function and inhibition of PI4Ks may enable the development of selective therapeutic strategies for infectious diseases while minimising off-target effects on host cells.

The immune system exists in perpetual co-evolution with pathogens, and microbial pathogenesis is inexorably linked to the cyclical interactions between the pathogen and the host. Because pathogens exploit the immune system in unique ways, the antimicrobial efficacy of any given immune process varies between pathogens, and the consequences of activation or inhibition of antimicrobial programs must be interpreted in the context of the given pathogen. An increasing body of literature shows that numerous facets of the immune system are tightly regulated by the circadian clock, with multiple immune processes demonstrating increased activity during certain times of the day. However, the field of circadian immunology has generally given its attention to unraveling the mechanism of circadian regulation and comparatively little attention to how these circadian oscillations may influence the ultimate outcome of diseases. Therefore, this review aims to interpret these findings in the context of a select number of clinically relevant pathogens: Salmonella enterica, Listeria monocytogenes, and Streptococcus pneumoniae. In this way, we hope to discuss the complex factors that determine how the circadian clock regulates disease progression.

Many postdocs work as leaders later in their career. But how do postdocs acquire the skills to become leaders? Postdocs from the international Marie Skłodowska–Curie leadership program (LEAD) at the University of Copenhagen postulate that supervision should be seen as an opportunity for training leadership skills. However, although every postdoc will supervise a student sooner or later, too many might find it a burden, which can lead to poor supervision and frustration. To help peers overcome problems in supervision, LEAD postdocs provide concrete tips for supervisors regarding planning, expectations alignment, and trust building. These tips can help supervisors establish a healthy, professional student–supervisor relationship that fosters the students' independence and ultimately leads to good science. Furthermore, the authors point out that the tasks related to supervision translate into leadership skills, such as delegation, decision-making, and relationship building. Hence, by focusing on becoming good supervisors, postdocs can prepare themselves for future leadership positions and provide a fruitful professional environment for students.