Small proteins modulate ion-channel-like ACD6 to regulate immunity in Arabidopsis thaliana
The ankyrin-repeat transmembrane protein ACD6 was identified two decades ago, but its exact biochemical function has remained enigmatic. Chen et al. show that ACD6 is a bona fide regulator of calcium influx using heterologous systems and calcium reporters in plants and that this activity can be further enhanced by a MHA1L peptide ligand. (Source: Molecular Cell)
Source: Molecular Cell - November 22, 2023 Category: Cytology Authors: Junbin Chen, Lei Li, Jong Hum Kim, Benjamin Neuh äuser, Mingyu Wang, Michael Thelen, Richard Hilleary, Yuan Chi, Luyang Wei, Kavita Venkataramani, Moises Exposito-Alonso, Chang Liu, Jakob Keck, A. Cristina Barragan, Rebecca Schwab, Ulrich Lutz, Zhen-Ming Tags: Article Source Type: research
Nuclear RNA catabolism controls endogenous retroviruses, gene expression asymmetry, and dedifferentiation
Torre et al. report a functional role of the RNA exosome and Integrator in regulating cell identity, ERV expression, and RNAPII elongation in embryonic stem cells. Disrupting either of these complexes promotes a totipotent-like 2CLC state, downregulating pluripotency genes, reducing transcriptional elongat ion, and primarily affecting long, multi-exonic genes. (Source: Molecular Cell)
Source: Molecular Cell - November 22, 2023 Category: Cytology Authors: Denis Torre, Yesai S. Fstkchyan, Jessica Sook Yuin Ho, Youngseo Cheon, Roosheel S. Patel, Emma J. Degrace, Slim Mzoughi, Megan Schwarz, Kevin Mohammed, Ji-Seon Seo, Raquel Romero-Bueno, Deniz Demircioglu, Dan Hasson, Weijing Tang, Sameehan U. Mahajani, La Tags: Article Source Type: research
Locus-specific proteome decoding reveals Fpt1 as a chromatin-associated negative regulator of RNA polymerase III assembly
van Breugel et al. decode the chromatin proteome of a single tRNA gene. They observe dynamic behavior of the transcription machinery and Fpt1. Fpt1 preferentially occupies regulated tRNA genes and promotes RNA polymerase III dynamics. These findings provide molecular insights into the differential regulation of tRNA genes. (Source: Molecular Cell)
Source: Molecular Cell - November 22, 2023 Category: Cytology Authors: Maria Elize van Breugel, Ila van Kruijsbergen, Chitvan Mittal, Cor Lieftink, Ineke Brouwer, Teun van den Brand, Roelof J.C. Kluin, Liesbeth Hoekman, Ren ée X. Menezes, Tibor van Welsem, Andrea Del Cortona, Muddassir Malik, Roderick L. Beijersbergen, Tine Tags: Article Source Type: research
Structural basis of RNA-induced autoregulation of the DExH-type RNA helicase maleless
Jagtap et al., combining structural and functional studies, show how the auxiliary domain dsRBD2 in DExH RNA helicase MLE regulates the helicase activity by undergoing large-scale conformation changes. These findings contribute to understanding the fundamental mechanics of auxiliary domains in MLE, which se rves as a model for its human ortholog and potential therapeutic target, DHX9. (Source: Molecular Cell)
Source: Molecular Cell - November 20, 2023 Category: Cytology Authors: Pravin Kumar Ankush Jagtap, Marisa M üller, Anna E. Kiss, Andreas W. Thomae, Karine Lapouge, Martin Beck, Peter B. Becker, Janosch Hennig Tags: Article Source Type: research
Nucleolus activity-dependent recruitment and biomolecular condensation by pH sensing
Aryan, Detr és et al. identify a compelling mechanism that illustrates how biochemical activities within biomolecular condensates facilitate the selective recruitment of their constituents. (Source: Molecular Cell)
Source: Molecular Cell - November 17, 2023 Category: Cytology Authors: Fardin Aryan, Diego Detr és, Claire C. Luo, Skylar X. Kim, Arish N. Shah, Michaela Bartusel, Ryan A. Flynn, Eliezer Calo Tags: Short article Source Type: research
EGFR promotes ALKBH5 nuclear retention to attenuate N6-methyladenosine and protect against ferroptosis in glioblastoma
Although growth receptor pathways commonly activate similar pathways, Lv et al. show that EGF signaling represses m6A levels in contrast to induction by PDGF. EGFR blocks ALKBH5 nuclear export, increasing m6A eraser function and suppression of ferroptosis through glutathione production. ALKBH5 inhibitors enhance the anti-tumor efficacy of EGFR or glutathione inhibitors. (Source: Molecular Cell)
Source: Molecular Cell - November 17, 2023 Category: Cytology Authors: Deguan Lv, Cuiqing Zhong, Deobrat Dixit, Kailin Yang, Qiulian Wu, Bhaskar Godugu, Briana C. Prager, Guofeng Zhao, Xiuxing Wang, Qi Xie, Shideng Bao, Chuan He, Dieter Henrik Heiland, Michael G. Rosenfeld, Jeremy N. Rich Tags: Article Source Type: research
Elucidation of E3 ubiquitin ligase specificity through proteome-wide internal degron mapping
(Molecular Cell 83, 3377 –3392.e1–e6; September 21, 2023) (Source: Molecular Cell)
Source: Molecular Cell - November 16, 2023 Category: Cytology Authors: Zhiqian Zhang, Brandon Sie, Aiquan Chang, Yumei Leng, Christopher Nardone, Richard T. Timms, Stephen J. Elledge Tags: Correction Source Type: research
Ran-Binding Protein 3 Phosphorylation Links the Ras and PI3-Kinase Pathways to Nucleocytoplasmic Transport
(Molecular Cell 29, 362 –375; February 15, 2008) (Source: Molecular Cell)
Source: Molecular Cell - November 16, 2023 Category: Cytology Authors: Sang-Oh Yoon, Sejeong Shin, Yuzhen Liu, Bryan A. Ballif, Michele S. Woo, Steven P. Gygi, John Blenis Tags: Editorial note Source Type: research
Targeted perturbation of signaling-driven condensates
Gui et al. propose a model for condensate perturbation through monomer saturation by short interacting peptides. Using β-catenin-binding peptides, they demonstrate that transcriptional condensates can be perturbed, leading to the inhibition of oncogenic WNT signaling. They expand their findings by targe ting the Hippo pathway, demonstrating applicability to other signaling pathways. (Source: Molecular Cell)
Source: Molecular Cell - November 16, 2023 Category: Cytology Authors: Tianshu Gui, Cassio Fleming, Caterina Manzato, Benjamin Bourgeois, Nafiseh Sirati, Jasper Heuer, Ioanna Papadionysiou, Daniel I. van Montfort, Merel van Gijzen, Lydia M.M. Smits, Boudewijn M.T. Burgering, Tobias Madl, Jurian Schuijers Tags: Article Source Type: research
The γ-secretase substrate proteome and its role in cell signaling regulation
The field has been lacking an unbiased approach for large-scale endogenous γ-secretase substrate identification. Hou et al. report a G-SECSI method and demonstrate that the γ-secretase substrate proteome is intimately connected to the intracellular signaling in microglia. γ-Secretase deficiency has profound effects on microglia in response to amyloid pathology. (Source: Molecular Cell)
Source: Molecular Cell - November 16, 2023 Category: Cytology Authors: Pengfei Hou, Magdalena Zielonka, Lutgarde Serneels, Anna Martinez-Muriana, Nicola Fattorelli, Leen Wolfs, Suresh Poovathingal, Dries T'Syen, Sriram Balusu, Tom Theys, Mark Fiers, Renzo Mancuso, Andrew J.M. Howden, Bart De Strooper Tags: Article Source Type: research
Active growth signaling promotes senescence and cancer cell sensitivity to CDK7 inhibition
Wilson et al. show that enhanced growth rate, a hallmark of cancer, plays a key role in a cells’ sensitivity to CDK7 inhibition, by driving a permanent cell division arrest via increasing cell size beyond a point of no return. This work can guide the use of CDK inhibitors in the clinic. (Source: Molecular Cell)
Source: Molecular Cell - November 16, 2023 Category: Cytology Authors: Gemma A. Wilson, Karla Vuina, Georgina Sava, Caroline Huard, Leticia Meneguello, Jasmin Coulombe-Huntington, Thierry Bertomeu, Rory J. Maizels, Josh Lauring, Janos Kriston-Vizi, Mike Tyers, Simak Ali, Cosetta Bertoli, Robertus A.M. de Bruin Tags: Article Source Type: research
CDK4/6 inhibitor-mediated cell overgrowth triggers osmotic and replication stress to promote senescence
CDK4/6 inhibitors, used to treat metastatic breast cancer, can have long-term anti-proliferative effects, even after patients finish treatment. Crozier et al. show that CDK4/6 inhibitors block cell proliferation but not growth. This causes cell overgrowth, leading to biphasic cellular stress responses that drive permanent cell-cycle withdrawal. (Source: Molecular Cell)
Source: Molecular Cell - November 16, 2023 Category: Cytology Authors: Lisa Crozier, Reece Foy, Rozita Adib, Ananya Kar, Jordan A. Holt, Aanchal U. Pareri, Juan Manuel Valverde, Rene Rivera, William A. Weston, Rona Wilson, Clement Regnault, Phil Whitfield, Mihaly Badonyi, Laura G. Bennett, Ellen G. Vernon, Amelia Gamble, Jos Tags: Article Source Type: research
Oncogenic signals prime cancer cells for toxic cell overgrowth during a G1 cell cycle arrest
Cell growth and the cell cycle must be coordinated to preserve cell viability. Foy et al. demonstrate that CDK4/6 inhibitors uncouple these two processes to drive excessive cellular overgrowth, DNA damage, and cell cycle exit. Oncogenic signals exacerbate these effects, likely contributing to cancer cell sensitivity to CDK4/6 inhibitors. (Source: Molecular Cell)
Source: Molecular Cell - November 16, 2023 Category: Cytology Authors: Reece Foy, Lisa Crozier, Aanchal U. Pareri, Juan Manuel Valverde, Ben Ho Park, Tony Ly, Adrian T. Saurin Tags: Article Source Type: research
Genome homeostasis defects drive enlarged cells into senescence
Manohar et al. studied how increased cell size—a hallmark of senescence—impairs long-term proliferation. Excess cell size activates p53-p21 signaling and impairs 53BP1 recruitment to DNA double-stranded breaks. This defect correlates with an impaired DNA damage response, DNA damage sensitivity, and genom ic instability, resulting in permanent cell-cycle exit. (Source: Molecular Cell)
Source: Molecular Cell - November 16, 2023 Category: Cytology Authors: Sandhya Manohar, Marianna E. Estrada, Federico Uliana, Karla Vuina, Patricia Moyano Alvarez, Robertus A.M. de Bruin, Gabriel E. Neurohr Tags: Article Source Type: research
Large-scale clustering of AlphaFold2 3D models shines light on the structure and function of proteins
Two recent studies exploited ultra-fast structural aligners and deep-learning approaches to cluster the protein structure space in the AlphaFold Database. Barrio-Hernandez et al. and Durairaj et al. uncovered fascinating new protein functions and structural features previously unknown. (Source: Molecular Cell)
Source: Molecular Cell - November 16, 2023 Category: Cytology Authors: Nicola Bordin, Andy M. Lau, Christine Orengo Tags: Spotlight Source Type: research
