journal
https://read.qxmd.com/read/38858602/k128-ubiquitination-constrains-ras-activity-by-expanding-its-binding-interface-with-gap-proteins
#1
JOURNAL ARTICLE
Wout Magits, Mikhail Steklov, Hyunbum Jang, Raj N Sewduth, Amir Florentin, Benoit Lechat, Aidana Sheryazdanova, Mingzhen Zhang, Michal Simicek, Gali Prag, Ruth Nussinov, Anna Sablina
The RAS pathway is among the most frequently activated signaling nodes in cancer. However, the mechanisms that alter RAS activity in human pathologies are not entirely understood. The most prevalent post-translational modification within the GTPase core domain of NRAS and KRAS is ubiquitination at lysine 128 (K128), which is significantly decreased in cancer samples compared to normal tissue. Here, we found that K128 ubiquitination creates an additional binding interface for RAS GTPase-activating proteins (GAPs), NF1 and RASA1, thus increasing RAS binding to GAP proteins and promoting GAP-mediated GTP hydrolysis...
June 10, 2024: EMBO Journal
https://read.qxmd.com/read/38858601/mcm8-interacts-with-ddx5-to-promote-r-loop-resolution
#2
JOURNAL ARTICLE
Canxin Wen, Lili Cao, Shuhan Wang, Weiwei Xu, Yongze Yu, Simin Zhao, Fan Yang, Zi-Jiang Chen, Shidou Zhao, Yajuan Yang, Yingying Qin
MCM8 has emerged as a core gene in reproductive aging and is crucial for meiotic homologous recombination repair. It also safeguards genome stability by coordinating the replication stress response during mitosis, but its function in mitotic germ cells remains elusive. Here we found that disabling MCM8 in mice resulted in proliferation defects of primordial germ cells (PGCs) and ultimately impaired fertility. We further demonstrated that MCM8 interacted with two known helicases DDX5 and DHX9, and loss of MCM8 led to R-loop accumulation by reducing the retention of these helicases at R-loops, thus inducing genome instability...
June 10, 2024: EMBO Journal
https://read.qxmd.com/read/38839993/multi-step-control-of-homologous-recombination-via-mec1-atr-suppresses-chromosomal-rearrangements
#3
JOURNAL ARTICLE
Bokun Xie, Ethan James Sanford, Shih-Hsun Hung, Mateusz Wagner, Wolf-Dietrich Heyer, Marcus B Smolka
The Mec1/ATR kinase is crucial for genome stability, yet the mechanism by which it prevents gross chromosomal rearrangements (GCRs) remains unknown. Here we find that in cells with deficient Mec1 signaling, GCRs accumulate due to the deregulation of multiple steps in homologous recombination (HR). Mec1 primarily suppresses GCRs through its role in activating the canonical checkpoint kinase Rad53, which ensures the proper control of DNA end resection. Upon loss of Rad53 signaling and resection control, Mec1 becomes hyperactivated and triggers a salvage pathway in which the Sgs1 helicase is recruited to sites of DNA lesions via the 911-Dpb11 scaffolds and phosphorylated by Mec1 to favor heteroduplex rejection and limit HR-driven GCR accumulation...
June 5, 2024: EMBO Journal
https://read.qxmd.com/read/38839992/whole-body-replacement-of-larval-myofibers-generates-permanent-adult-myofibers-in-zebrafish
#4
JOURNAL ARTICLE
Uday Kumar, Chun-Yi Fang, Hsiao-Yuh Roan, Shao-Chun Hsu, Chung-Han Wang, Chen-Hui Chen
Drastic increases in myofiber number and size are essential to support vertebrate post-embryonic growth. However, the collective cellular behaviors that enable these increases have remained elusive. Here, we created the palmuscle myofiber tagging and tracking system for in toto monitoring of the growth and fates of ~5000 fast myofibers in developing zebrafish larvae. Through live tracking of individual myofibers within the same individuals over extended periods, we found that many larval myofibers readily dissolved during development, enabling the on-site addition of new and more myofibers...
June 5, 2024: EMBO Journal
https://read.qxmd.com/read/38839991/functional-diversity-among-cardiolipin-binding-sites-on-the-mitochondrial-adp-atp-carrier
#5
JOURNAL ARTICLE
Nanami Senoo, Dinesh K Chinthapalli, Matthew G Baile, Vinaya K Golla, Bodhisattwa Saha, Abraham O Oluwole, Oluwaseun B Ogunbona, James A Saba, Teona Munteanu, Yllka Valdez, Kevin Whited, Macie S Sheridan, Dror Chorev, Nathan N Alder, Eric R May, Carol V Robinson, Steven M Claypool
Lipid-protein interactions play a multitude of essential roles in membrane homeostasis. Mitochondrial membranes have a unique lipid-protein environment that ensures bioenergetic efficiency. Cardiolipin (CL), the signature mitochondrial lipid, plays multiple roles in promoting oxidative phosphorylation (OXPHOS). In the inner mitochondrial membrane, the ADP/ATP carrier (AAC in yeast; adenine nucleotide translocator, ANT in mammals) exchanges ADP and ATP, enabling OXPHOS. AAC/ANT contains three tightly bound CLs, and these interactions are evolutionarily conserved...
June 5, 2024: EMBO Journal
https://read.qxmd.com/read/38834854/author-correction-rad54-and-rdh54-occupy-spatially-and-functionally-distinct-sites-within-the-rad51-ssdna-presynaptic-complex
#6
J Brooks Crickard, Youngho Kwon, Patrick Sung, Eric C Greene
No abstract text is available yet for this article.
June 4, 2024: EMBO Journal
https://read.qxmd.com/read/38834853/parp14-and-parp9-dtx3l-regulate-interferon-induced-adp-ribosylation
#7
JOURNAL ARTICLE
Pulak Kar, Chatrin Chatrin, Nina Đukić, Osamu Suyari, Marion Schuller, Kang Zhu, Evgeniia Prokhorova, Nicolas Bigot, Juraj Ahel, Jonas Damgaard Elsborg, Michael L Nielsen, Tim Clausen, Sébastien Huet, Mario Niepel, Sumana Sanyal, Dragana Ahel, Rebecca Smith, Ivan Ahel
PARP-catalysed ADP-ribosylation (ADPr) is important in regulating various cellular pathways. Until recently, PARP-dependent mono-ADP-ribosylation has been poorly understood due to the lack of sensitive detection methods. Here, we utilised an improved antibody to detect mono-ADP-ribosylation. We visualised endogenous interferon (IFN)-induced ADP-ribosylation and show that PARP14 is a major enzyme responsible for this modification. Fittingly, this signalling is reversed by the macrodomain from SARS-CoV-2 (Mac1), providing a possible mechanism by which Mac1 counteracts the activity of antiviral PARPs...
June 4, 2024: EMBO Journal
https://read.qxmd.com/read/38834852/parp14-is-regulated-by-the-parp9-dtx3l-complex-and-promotes-interferon-%C3%AE-induced-adp-ribosylation
#8
JOURNAL ARTICLE
Victoria Chaves Ribeiro, Lilian Cristina Russo, Nícolas Carlos Hoch
Protein ADP-ribosylation plays important but ill-defined roles in antiviral signalling cascades such as the interferon response. Several viruses of clinical interest, including coronaviruses, express hydrolases that reverse ADP-ribosylation catalysed by host enzymes, suggesting an important role for this modification in host-pathogen interactions. However, which ADP-ribosyltransferases mediate host ADP-ribosylation, what proteins and pathways they target and how these modifications affect viral infection and pathogenesis is currently unclear...
June 4, 2024: EMBO Journal
https://read.qxmd.com/read/38831123/inheritance-of-h3k9-methylation-regulates-genome-architecture-in-drosophila-early-embryos
#9
JOURNAL ARTICLE
Nazerke Atinbayeva, Iris Valent, Fides Zenk, Eva Loeser, Michael Rauer, Shwetha Herur, Piergiuseppe Quarato, Giorgos Pyrowolakis, Alejandro Gomez-Auli, Gerhard Mittler, Germano Cecere, Sylvia Erhardt, Guido Tiana, Yinxiu Zhan, Nicola Iovino
Constitutive heterochromatin is essential for transcriptional silencing and genome integrity. The establishment of constitutive heterochromatin in early embryos and its role in early fruitfly development are unknown. Lysine 9 trimethylation of histone H3 (H3K9me3) and recruitment of its epigenetic reader, heterochromatin protein 1a (HP1a), are hallmarks of constitutive heterochromatin. Here, we show that H3K9me3 is transmitted from the maternal germline to the next generation. Maternally inherited H3K9me3, and the histone methyltransferases (HMT) depositing it, are required for the organization of constitutive heterochromatin: early embryos lacking H3K9 methylation display de-condensation of pericentromeric regions, centromere-centromere de-clustering, mitotic defects, and nuclear shape irregularities, resulting in embryo lethality...
June 3, 2024: EMBO Journal
https://read.qxmd.com/read/38831122/spatiotemporally-distinct-responses-to-mechanical-forces-shape-the-developing-seed-of-arabidopsis
#10
JOURNAL ARTICLE
Amélie Bauer, Olivier Ali, Camille Bied, Sophie Bœuf, Simone Bovio, Adrien Delattre, Gwyneth Ingram, John F Golz, Benoit Landrein
Organ morphogenesis depends on mechanical interactions between cells and tissues. These interactions generate forces that can be sensed by cells and affect key cellular processes. However, how mechanical forces, together with biochemical signals, contribute to the shaping of complex organs is still largely unclear. We address this question using the seed of Arabidopsis as a model system. We show that seeds first experience a phase of rapid anisotropic growth that is dependent on the response of cortical microtubule (CMT) to forces, which guide cellulose deposition according to shape-driven stresses in the outermost layer of the seed coat...
June 3, 2024: EMBO Journal
https://read.qxmd.com/read/38822137/yipf3-and-yipf4-regulate-autophagic-turnover-of-the-golgi-apparatus
#11
JOURNAL ARTICLE
Shinri Kitta, Tatsuya Kaminishi, Momoko Higashi, Takayuki Shima, Kohei Nishino, Nobuhiro Nakamura, Hidetaka Kosako, Tamotsu Yoshimori, Akiko Kuma
The degradation of organelles by autophagy is essential for cellular homeostasis. The Golgi apparatus has recently been demonstrated to be degraded by autophagy, but little is known about how the Golgi is recognized by the forming autophagosome. Using quantitative proteomic analysis and two novel Golgiphagy reporter systems, we found that the five-pass transmembrane Golgi-resident proteins YIPF3 and YIPF4 constitute a Golgiphagy receptor. The interaction of this complex with LC3B, GABARAP, and GABARAPL1 is dependent on a LIR motif within YIPF3 and putative phosphorylation sites immediately upstream; the stability of the complex is governed by YIPF4...
May 31, 2024: EMBO Journal
https://read.qxmd.com/read/38816652/il-27-maintains-cytotoxic-ly6c-%C3%AE-%C3%AE-t-cells-that-arise-from-immature-precursors
#12
JOURNAL ARTICLE
Robert Wiesheu, Sarah C Edwards, Ann Hedley, Holly Hall, Marie Tosolini, Marcelo Gregorio Filho Fares da Silva, Nital Sumaria, Suzanne M Castenmiller, Leyma Wardak, Yasmin Optaczy, Amy Lynn, David G Hill, Alan J Hayes, Jodie Hay, Anna Kilbey, Robin Shaw, Declan Whyte, Peter J Walsh, Alison M Michie, Gerard J Graham, Anand Manoharan, Christina Halsey, Karen Blyth, Monika C Wolkers, Crispin Miller, Daniel J Pennington, Gareth W Jones, Jean-Jacques Fournie, Vasileios Bekiaris, Seth B Coffelt
In mice, γδ-T lymphocytes that express the co-stimulatory molecule, CD27, are committed to the IFNγ-producing lineage during thymic development. In the periphery, these cells play a critical role in host defense and anti-tumor immunity. Unlike αβ-T cells that rely on MHC-presented peptides to drive their terminal differentiation, it is unclear whether MHC-unrestricted γδ-T cells undergo further functional maturation after exiting the thymus. Here, we provide evidence of phenotypic and functional diversity within peripheral IFNγ-producing γδ T cells...
May 30, 2024: EMBO Journal
https://read.qxmd.com/read/38811853/trp14-is-the-rate-limiting-enzyme-for-intracellular-cystine-reduction-and-regulates-proteome-cysteinylation
#13
JOURNAL ARTICLE
Pablo Martí-Andrés, Isabela Finamor, Isabel Torres-Cuevas, Salvador Pérez, Sergio Rius-Pérez, Hildegard Colino-Lage, David Guerrero-Gómez, Esperanza Morato, Anabel Marina, Patrycja Michalska, Rafael León, Qing Cheng, Eszter Petra Jurányi, Klaudia Borbényi-Galambos, Iván Millán, Péter Nagy, Antonio Miranda-Vizuete, Edward E Schmidt, Antonio Martínez-Ruiz, Elias Sj Arnér, Juan Sastre
It has remained unknown how cells reduce cystine taken up from the extracellular space, which is a required step for further utilization of cysteine in key processes such as protein or glutathione synthesis. Here, we show that the thioredoxin-related protein of 14 kDa (TRP14, encoded by TXNDC17) is the rate-limiting enzyme for intracellular cystine reduction. When TRP14 is genetically knocked out, cysteine synthesis through the transsulfuration pathway becomes the major source of cysteine in human cells, and knockout of both pathways becomes lethal in C...
May 29, 2024: EMBO Journal
https://read.qxmd.com/read/38811852/higher-order-structure-and-proteoforms-of-co-occurring-c4b-binding-protein-assemblies-in-human-serum
#14
JOURNAL ARTICLE
Tereza Kadavá, Johannes F Hevler, Sofia Kalaidopoulou Nteak, Victor C Yin, Juergen Strasser, Johannes Preiner, Albert Jr Heck
The complement is a conserved cascade that plays a central role in the innate immune system. To maintain a delicate equilibrium preventing excessive complement activation, complement inhibitors are essential. One of the major fluid-phase complement inhibitors is C4b-binding protein (C4BP). Human C4BP is a macromolecular glycoprotein composed of two distinct subunits, C4BPα and C4BPβ. These associate with vitamin K-dependent protein S (ProS) forming an ensemble of co-occurring higher-order structures...
May 29, 2024: EMBO Journal
https://read.qxmd.com/read/38811851/chromatin-modifier-hmga2-promotes-adult-hematopoietic-stem-cell-function-and-blood-regeneration-in-stress-conditions
#15
JOURNAL ARTICLE
Sho Kubota, Yuqi Sun, Mariko Morii, Jie Bai, Takako Ideue, Mayumi Hirayama, Supannika Sorin, Eerdunduleng, Takako Yokomizo-Nakano, Motomi Osato, Ai Hamashima, Mihoko Iimori, Kimi Araki, Terumasa Umemoto, Goro Sashida
The molecular mechanisms governing the response of hematopoietic stem cells (HSCs) to stress insults remain poorly defined. Here, we investigated effects of conditional knock-out or overexpression of Hmga2 (High mobility group AT-hook 2), a transcriptional activator of stem cell genes in fetal HSCs. While Hmga2 overexpression did not affect adult hematopoiesis under homeostasis, it accelerated HSC expansion in response to injection with 5-fluorouracil (5-FU) or in vitro treatment with TNF-α. In contrast, HSC and megakaryocyte progenitor cell numbers were decreased in Hmga2 KO animals...
May 29, 2024: EMBO Journal
https://read.qxmd.com/read/38806660/a-systematic-exploration-of-bacterial-form-i-rubisco-maximal-carboxylation-rates
#16
JOURNAL ARTICLE
Benoit de Pins, Lior Greenspoon, Yinon M Bar-On, Melina Shamshoum, Roee Ben-Nissan, Eliya Milshtein, Dan Davidi, Itai Sharon, Oliver Mueller-Cajar, Elad Noor, Ron Milo
Autotrophy is the basis for complex life on Earth. Central to this process is rubisco-the enzyme that catalyzes almost all carbon fixation on the planet. Yet, with only a small fraction of rubisco diversity kinetically characterized so far, the underlying biological factors driving the evolution of fast rubiscos in nature remain unclear. We conducted a high-throughput kinetic characterization of over 100 bacterial form I rubiscos, the most ubiquitous group of rubisco sequences in nature, to uncover the determinants of rubisco's carboxylation velocity...
May 28, 2024: EMBO Journal
https://read.qxmd.com/read/38806659/neurons-dispose-of-hyperactive-kinesin-into-glial-cells-for-clearance
#17
JOURNAL ARTICLE
Chao Xie, Guanghan Chen, Ming Li, Peng Huang, Zhe Chen, Kexin Lei, Dong Li, Yuhe Wang, Augustine Cleetus, Mohamed Aa Mohamed, Punam Sonar, Wei Feng, Zeynep Ökten, Guangshuo Ou
Microtubule-based kinesin motor proteins are crucial for intracellular transport, but their hyperactivation can be detrimental for cellular functions. This study investigated the impact of a constitutively active ciliary kinesin mutant, OSM-3CA, on sensory cilia in C. elegans. Surprisingly, we found that OSM-3CA was absent from cilia but underwent disposal through membrane abscission at the tips of aberrant neurites. Neighboring glial cells engulf and eliminate the released OSM-3CA, a process that depends on the engulfment receptor CED-1...
May 28, 2024: EMBO Journal
https://read.qxmd.com/read/38806658/lc3-associated-phagocytosis-of-neutrophils-triggers-tumor-ferroptotic-cell-death-in-glioblastoma
#18
JOURNAL ARTICLE
Tong Lu, Patricia P Yee, Stephen Y Chih, Miaolu Tang, Han Chen, Dawit G Aregawi, Michael J Glantz, Brad E Zacharia, Hong-Gang Wang, Wei Li
Necrosis in solid tumors is commonly associated with poor prognostic but how these lesions expand remains unclear. Studies have found that neutrophils associate with and contribute to necrosis development in glioblastoma by inducing tumor cell ferroptosis through transferring myeloperoxidase-containing granules. However, the mechanism of neutrophilic granule transfer remains elusive. We performed an unbiased small molecule screen and found that statins inhibit neutrophil-induced tumor cell death by blocking the neutrophilic granule transfer...
May 28, 2024: EMBO Journal
https://read.qxmd.com/read/38778156/the-immune-response-to-rna-suppresses-nucleic-acid-synthesis-by-limiting-ribose-5-phosphate
#19
JOURNAL ARTICLE
Pushpak Bhattacharjee, Die Wang, Dovile Anderson, Joshua N Buckler, Eveline de Geus, Feng Alex Yan, Galina Polekhina, Ralf Schittenhelm, Darren J Creek, Lawrence D Harris, Anthony J Sadler
During infection viruses hijack host cell metabolism to promote their replication. Here, analysis of metabolite alterations in macrophages exposed to poly I:C recognises that the antiviral effector Protein Kinase RNA-activated (PKR) suppresses glucose breakdown within the pentose phosphate pathway (PPP). This pathway runs parallel to central glycolysis and is critical to producing NADPH and pentose precursors for nucleotides. Changes in metabolite levels between wild-type and PKR-ablated macrophages show that PKR controls the generation of ribose 5-phosphate, in a manner distinct from its established function in gene expression but dependent on its kinase activity...
May 22, 2024: EMBO Journal
https://read.qxmd.com/read/38778155/circadian-regulation-of-macromolecular-complex-turnover-and-proteome-renewal
#20
JOURNAL ARTICLE
Estere Seinkmane, Anna Edmondson, Sew Y Peak-Chew, Aiwei Zeng, Nina M Rzechorzek, Nathan R James, James West, Jack Munns, David Cs Wong, Andrew D Beale, John S O'Neill
Although costly to maintain, protein homeostasis is indispensable for normal cellular function and long-term health. In mammalian cells and tissues, daily variation in global protein synthesis has been observed, but its utility and consequences for proteome integrity are not fully understood. Using several different pulse-labelling strategies, here we gain direct insight into the relationship between protein synthesis and abundance proteome-wide. We show that protein degradation varies in-phase with protein synthesis, facilitating rhythms in turnover rather than abundance...
May 22, 2024: EMBO Journal
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