cell autonomous innate immunity by proteasome derived defence peptides proteasomes can process proteins into antimicrobial peptides - Psme3 Cell-autonomous innate immunity by proteasome-derived defence peptides Cell-Autonomous Innate Immunity by Proteasome-Derived Defence Peptides: A Cellular Defense Revelation

Ubiquitinproteasomesystem Recent groundbreaking research has illuminated a previously unrecognized facet of the innate immune system, revealing that proteasomes, the cellular machinery responsible for protein degradation, can also serve as a potent arsenal against bacterial invaders. This discovery, detailed in the prestigious journal *Nature* (DOI: 10.2025年4月6日—3月5日《Nature》杂志的研究报道“Cell-autonomous innate immunity by proteasome-derived defence peptides”，揭示：人体细胞内默默运转的"蛋白质碎纸机"—— ...1038/s41586-025-08615-w) in March 2025, unveils a mechanism of cell-autonomous innate immunity where proteasome-derived defence peptides are generated to directly combat pathogens. This paradigm shift in our understanding of immune defense highlights the intricate and multifaceted roles of cellular components in maintaining organismal health.Cell-autonomous innate immunity by proteasome-derived defence peptides· Karin Goldberg ·, Arseniy Lobov ·, Paola Antonello ·, Merav D. Shmueli ·, Idan Yakir ·, ...

The research, spearheaded by teams including those led by Professors Yifat Merbl and Karin Goldberg, demonstrates that proteasomes are not merely waste disposal units but are actively involved in the constitutive and bacterial-induced generation of defence peptides. These peptides, which exhibit strong anti-microbial properties, are capable of impeding bacterial growth both *in vitro* and *in vivo*. This finding is particularly significant as antimicrobial peptides are known to serve as a crucial first line of defence against invading pathogens, acting even before the more specialized adaptive immune system can mount a responseIn this study, we uncover a previously unknown role for theproteasomeininnateimmune defense: generating antimicrobialpeptidesthat can directly disrupt .... The discovery of proteasome-derived antimicrobial peptides adds a new dimension to this critical early defense strategy.

The proteasome, a large protein complex found in all eukaryotic cells, is primarily known for its role in the ubiquitin-proteasome system, which regulates protein turnover and eliminates damaged or unwanted proteins. However, this new research reveals that protein degradation via proteasomes plays an important role in immune signaling and antigen presentation in ways previously unappreciated.Scientists discover new part of the immune system. ... Specifically, the proteasome can process proteins into antimicrobial peptides (AMPs), effectively transforming cellular "waste" into antibiotics2025年5月12日—本文，我们揭示了蛋白酶体在组成性和细菌诱导的防御肽生成中的作用，这些防御肽通过破坏细菌膜来阻止细菌在体外和体内的生长。通过对蛋白质组范围的蛋白酶体 .... This capability is not limited to situations of active infection; the proteasome contributes to this defence mechanism even under basal conditions, highlighting its constitutive role in innate immunity.An antibiotic arsenal in anti-bacterial innate immunity.

This newly identified mechanism allows immune cells and indeed, all cells, to mount a direct defence against intracellular pathogen invasion. The cell-autonomous nature of this immunity means that individual cells can protect themselves without necessarily relying on the broader systemic immune response. This intrinsic protective capacity is mediated by the proteasome-derived peptides, which have been shown to directly disrupt bacterial membranes, a key mechanism for killing bacteria. This revelation opens up a new frontier for understanding how cells defend themselves and suggests novel therapeutic avenues for combating bacterial infectionsCell-autonomous innate immunity by proteasome-derived ....

The implications of this discovery are far-reaching. The ability of proteasomes to generate derived peptides with antimicrobial properties suggests that these proteasome-derived defence peptides could represent a new class of therapeutics. The research indicates that these derived peptides exhibit antimicrobial properties and contribute to an autonomous immune response, positioning the proteasome as a vital player in innate immunity.2025年4月6日—3月5日《Nature》杂志的研究报道“Cell-autonomous innate immunity by proteasome-derived defence peptides”，揭示：人体细胞内默默运转的"蛋白质碎纸机"—— ... Furthermore, understanding how these proteasome-derived peptides are generated and function could lead to the development of personalized medicine approaches, leveraging the body's own defense mechanisms.

The study published in *Nature* provides detailed insights into the process, identifying specific peptides released during protein breakdown that possess bactericidal capabilities. This work builds upon existing knowledge of cell-autonomous innate immunity by demonstrating a novel effector mechanism. While previous research focused on other aspects of protein degradation via proteasomes, this study pivots to highlight its direct role in generating defence peptides....cell-autonomous innate immunity, mediated by proteasome-derived defense peptides. ... innate immunity by proteasome-derived defence peptides ... The identification of these proteasome-derived peptides in biological fluids, such as blood and wound fluid, further supports their *in vivo* relevance.

In essence, the proteasome acts as an "antibiotic factory" within our cells, continuously producing defence peptides that contribute to cell-autonomous innate immunity. This discovery not only deepens our comprehension of the fundamental workings of the immune system but also presents exciting possibilities for future therapeutic strategies against antibiotic-resistant bacteria. The proteasome has emerged as a hidden warrior, equipped with an arsenal of derived peptides ready to defend the cell from microbial threats.研究发现由蛋白酶体衍生的防御肽引起的细胞自主先天免疫 - 新闻 This research, focusing on cell-autonomous innate immunity, mediated by proteasome-derived defense peptides, marks a significant advancement in the field of immunology and infectious disease....cell-autonomous innate immunity, mediated by proteasome-derived defense peptides. ... innate immunity by proteasome-derived defence peptides ...