Unlocking the EGFR-mediated epitranscriptome: A pathway to novel therapies
In this issue, Lv et al.1 explore EGFR-driven epitranscriptomic reprogramming in glioblastoma, revealing the pivotal role of the EGFR-ALKBH5-GCLM axis in ferroptosis protection. Their findings offer mechanistic insight and therapeutic strategies involving novel combination targets to enhance tumor responses. (Source: Molecular Cell)
Source: Molecular Cell - December 7, 2023 Category: Cytology Authors: Jovanka Gencel-Augusto, Trever G. Bivona Tags: Preview Source Type: research
Atypical K6-ubiquitin chains mobilize p97/VCP and the proteasome to resolve formaldehyde-induced RNA-protein crosslinks
In this issue of Molecular Cell, Rahmanto et al.1 and Zhao et al.2 demonstrate that RNA-protein crosslinks contribute to formaldehyde toxicity by blocking protein synthesis. Furthermore, they identify a ubiquitin-mediated degradation system for RNA-protein crosslink resolution in eukaryotes. (Source: Molecular Cell)
Source: Molecular Cell - December 7, 2023 Category: Cytology Authors: Wei Song, Kristijan Ramadan Tags: Preview Source Type: research
Meet the Authors: Fardin Aryan, Diego Detr és, and Eliezer Calo
We talk to co-first authors Fardin Aryan and Diego Detr és along with lead contact Eliezer Calo about their paper “Nucleolus activity-dependent recruitment and biomolecular condensation by pH sensing” (this issue of Molecular Cell), what drew them to a career in science, and overcoming challenges posed by the global pandemic. (Source: Molecular Cell)
Source: Molecular Cell - December 7, 2023 Category: Cytology Authors: Eliezer Calo, Diego Detr és, Fardin Aryan Tags: Q & A Source Type: research
ER chaperones use a protein folding and quality control glyco-code
N-glycans act as quality control tags by recruiting endoplasmic reticulum lectin chaperones to assist protein maturation. The location and composition of N-glycans (glyco-code) are key to the molecular chaperone-selection process. Our study illustrates how serpins utilize N-glycan presence and location to direct their proper folding, quality control, and trafficking. (Source: Molecular Cell)
Source: Molecular Cell - December 4, 2023 Category: Cytology Authors: Kevin P. Guay, Haiping Ke, Nathan P. Canniff, Gracie T. George, Stephen J. Eyles, Malaiyalam Mariappan, Joseph N. Contessa, Anne Gershenson, Lila M. Gierasch, Daniel N. Hebert Tags: Article Source Type: research
Dual allosteric modulation of voltage and calcium sensitivities of the Slo1-LRRC channel complex
Yamanouchi and Kasuya et al. elucidate the mechanism for dual allosteric modulation of Ca2+/voltage sensitivity of Slo1 by LRRC26 from Slo1-LRRC26 complex structures. LRRC26 stabilizes the active conformations of voltage sensors and Ca2+ sensors through its transmembrane helix and intracellular Arg cluster. Structures fur ther provide insights into all-or-none gating modulation by LRRC26. (Source: Molecular Cell)
Source: Molecular Cell - November 29, 2023 Category: Cytology Authors: Daichi Yamanouchi, Go Kasuya, Koichi Nakajo, Yoshiaki Kise, Osamu Nureki Tags: Article Source Type: research
Boveri and beyond: Chromothripsis and genomic instability from mitotic errors
Chromothripsis drives rapid genome evolution through the extensive shattering of mis-segregated chromosomes. This review discusses the cell cycle checkpoints that protect against mitotic errors, how mis-segregated chromosomes entrapped in abnormal nuclear structures undergo shattering, and the DNA damage response mechanisms that reassemble shattered chromosomes to generate complex cancer genome rearrangements. (Source: Molecular Cell)
Source: Molecular Cell - November 28, 2023 Category: Cytology Authors: Alice Mazzagatti, Justin L. Engel, Peter Ly Tags: Review Source Type: research
Regulation of antioxidants in cancer
The paradoxical role of antioxidants in cancer has been a matter of intense debate in recent years. Here, we highlight the latest breakthroughs that shed light on the molecular mechanisms by which antioxidants are regulated in cancer to impact their initiation, progression, and metastatic capabilities. (Source: Molecular Cell)
Source: Molecular Cell - November 28, 2023 Category: Cytology Authors: Fabio Hecht, Marco Zocchi, Fatemeh Alimohammadi, Isaac S. Harris Tags: Perspective Source Type: research
A direct interaction between CPF and RNA Pol II links RNA 3 ′ end processing to transcription
The nature of the coupling between transcription and RNA 3 ′ end processing has remained elusive. Carminati et al. report that the cleavage and polyadenylation factor (CPF) binds and dephosphorylates RNA Pol II in vitro, which promotes RNA Pol II dimerization. Dimerization is incompatible with elongation factor binding, suggesting a potential role in te rmination. (Source: Molecular Cell)
Source: Molecular Cell - November 28, 2023 Category: Cytology Authors: Manuel Carminati, Juan B. Rodr íguez-Molina, M. Cemre Manav, Dom Bellini, Lori A. Passmore Tags: Article Source Type: research
Epigenetic pioneering by SWI/SNF family remodelers
The structure and activities of SWI/SNF family nucleosome remodeling complexes may reconcile the apparent stability of open chromatin with the brief residence times for pioneer factor transcription factor engagement with chromatin. Recent studies also implicate SWI/SNF family remodelers in transient interactions between enhancers and the promoters that they regulate. (Source: Molecular Cell)
Source: Molecular Cell - November 27, 2023 Category: Cytology Authors: Kami Ahmad, Sandipan Brahma, Steven Henikoff Tags: Perspective Source Type: research
m6A modification negatively regulates translation by switching mRNA from polysome to P-body via IGF2BP3
Shan et al. discovered that the m6A-IGF2BP3 axis regulates mRNA partitioning in HeLa cells. mRNAs enriched in the P-bodies are hyper-m6A-methylated, whereas those associated with polysomes are less methylated. Loss of m6A switches mRNAs from P-bodies to polysomes, whereas the m6A reader IGF2BP3 can drive target mRNAs to P-bodies. (Source: Molecular Cell)
Source: Molecular Cell - November 27, 2023 Category: Cytology Authors: Ting Shan, Feiyan Liu, Miaomiao Wen, Zonggui Chen, Shaopeng Li, Yafen Wang, Hong Cheng, Yu Zhou Tags: Article Source Type: research
CPT1A induction following epigenetic perturbation promotes MAVS palmitoylation and activation to potentiate antitumor immunity
Epigenetic treatment is now being explored to improve cancer immunotherapy. Zhang et al. report that CPT1A in tumor cells enables, and its further elevation enhances, the immunostimulatory effect of epigenetic treatment. CPT1A recruits ZDHHC4 to palmitoylate MAVS, which mitigates MAVS degradation and promotes its activation, thereby elevating the IFN-I response. (Source: Molecular Cell)
Source: Molecular Cell - November 27, 2023 Category: Cytology Authors: Guiheng Zhang, Peishan Jiang, Wen Tang, Yunyi Wang, Fengqi Qiu, Jie An, Yuping Zheng, Dandan Wu, Jianya Zhou, Dante Neculai, Yang Shi, Wanqiang Sheng Tags: Article Source Type: research
SMURF2 predisposes cancer cell toward ferroptosis in GPX4-independent manners by promoting GSTP1 degradation
By analyzing differentially expressed proteins in the early stages of ferroptosis, Zhang et al. identify a GPX4-independent ferroptosis regulatory mechanism mediated by the E3 ligase SUMRF2-regulated degradation of GSTP1. Both GST and selenium-independent GPx activities of GSTP1 are essential for ferroptosis protection. Modulation of SMURF2/GSTP1 sensitizes cancer cells to ferroptosis. (Source: Molecular Cell)
Source: Molecular Cell - November 27, 2023 Category: Cytology Authors: Wenxin Zhang, Junren Dai, Guixue Hou, Hao Liu, Shanliang Zheng, Xingwen Wang, Qingyu Lin, Yi Zhang, Minqiao Lu, Yafan Gong, Zhiyuan Xiang, Yan Yu, Ying Hu Tags: Article Source Type: research
Unbiased interrogation of functional lysine residues in human proteome
Bao et al. establish a CRISPR strategy for unbiasedly probing functional amino acid residues at the genome scale. They systematically survey the functional lysine residues that affect cell fitness. Novel mechanisms that govern the cell cycle via lysine residues are unraveled, and clinically significant l ysine mutations are identified. (Source: Molecular Cell)
Source: Molecular Cell - November 22, 2023 Category: Cytology Authors: Ying Bao, Qian Pan, Ping Xu, Zhiheng Liu, Zhixuan Zhang, Yongshuo Liu, Yiyuan Xu, Ying Yu, Zhuo Zhou, Wensheng Wei Tags: Resource Source Type: research
IntS6 and the Integrator phosphatase module tune the efficiency of select premature transcription termination events
Fujiwara et al. show that the phosphatase module of the Integrator complex is differentially required for transcription termination across Drosophila gene loci. When protein phosphatase 2A subunits are limiting, Integrator complex function is blocked at a subset of protein-coding genes, yet snRNA processing a nd transcription attenuation of other loci continue. (Source: Molecular Cell)
Source: Molecular Cell - November 22, 2023 Category: Cytology Authors: Rina Fujiwara, Si-Nan Zhai, Dongming Liang, Aayushi P. Shah, Matthew Tracey, Xu-Kai Ma, Christopher J. Fields, Mar ía Saraí Mendoza-Figueroa, Michele C. Meline, Deirdre C. Tatomer, Li Yang, Jeremy E. Wilusz Tags: Article Source Type: research
Structural insights into the assembly and mechanism of mpox virus DNA polymerase complex F8-A22-E4-H5
Wang et al. determined several structures of MPXV F8-A22-E4 and F8-A22-E4-H5 complexes, providing 3D snapshots for the functional cycle of the polymerase complex. Structural and functional analyses suggest a functional coupling between E4-mediated base-excision and F8-catalyzed DNA synthesis and pinpoint a possible role of processivity for the viral factor H5. (Source: Molecular Cell)
Source: Molecular Cell - November 22, 2023 Category: Cytology Authors: Xiaohan Wang, Liangwen Ma, Ningning Li, Ning Gao Tags: Article Source Type: research
