抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis. The pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation.

mTOR Signaling in Growth Control and Disease

mTOR signaling in growth control and disease.

mTOR Signaling in Growth, Metabolism, and Disease.

In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

/pdf/biological-properties-of-extracellular-vesicles-and-their-bef7axtqvb.pdf

Biological properties of extracellular vesicles and their physiological functions

Nucleus to Mitochondria: Lost in Transcription, Found in Translation

Protein synthesis is elevated in many cancers ( 1 ). To cope with increased protein load and protein folding defects caused by genetic abnormalities, malignant cells bolster their chaperone system. Heat-shock transcription factor 1 (HSF1) is a major activator of chaperone-encoding genes. In cancer cells, HSF1 also affects the transcription of genes that are implicated in tumorigenesis ( 2 ), thereby shaping the “malignant transcriptome.” On page 250 of this issue, Santagata et al. ( 3 ) suggest that HSF1 acts as a central node of a regulatory network that “senses” messenger RNA (mRNA) translation rates and enables malignant cells to respond to increased protein loads by reprogramming transcription.

https://science.sciencemag.org/content/sci/341/6143/242.full.pdf

Trans-HSF1 Express

/pdf/the-mitochondrial-pyruvate-carrier-complex-potentiates-the-12gwzmez.pdf

The mitochondrial pyruvate carrier complex potentiates the efficacy of proteasome inhibitors in multiple myeloma.

Summary Mammalian cells have to adapt to environmental challenges that range from mild to severe stress. While the cellular response to mild stress has been widely studied, how cells respond to severe stress remains unclear. We show here that under severe stress conditions, cells induce a transient hibernation-like mechanism that anticipates recovery. We demonstrate that this Adaptive Pausing Response (APR) is a coordinated cellular response that limits ATP supply and consumption though mitochondrial fragmentation and widespread pausing of mRNA translation. This pausing is accomplished by ribosome stalling at translation initiation codons, which keeps mRNAs poised to resume translation upon recovery from severe stress. We further show that recovery from severe stress involves adaptive ISR (Integrated Stress Response) signaling that in turn permits cell cycle progression, resumption of growth, and reversal of mitochondria fragmentation. Our findings indicate that cells can respond to severe stress through the APR, a mechanism that preserves vital elements of cellular function under harsh environmental conditions.

https://biorxiv.org/content/10.1101/2020.10.10.334375v1.full.pdf

Adaptive translational pausing is a hallmark of the cellular response to severe environmental stress

Members of the MYC family of oncogenes are master regulators of mRNA translation. In this issue of JEM, Singh et al. (https://doi.org/10.1084/jem.20181726) demonstrate that c-Myc governs protein synthesis in lymphoma cells by interfering with SRSF1- and RBM42-mediated suppression of mRNA translation and by altering selection of translation initiation sites.

/pdf/c-myc-steers-translation-in-lymphoma-qk3pfj5b6a.pdf

Ivan Topisirovic

Papers

Nucleus to Mitochondria: Lost in Transcription, Found in Translation

Trans-HSF1 Express

The mitochondrial pyruvate carrier complex potentiates the efficacy of proteasome inhibitors in multiple myeloma.

Adaptive translational pausing is a hallmark of the cellular response to severe environmental stress

c-Myc steers translation in lymphoma