Journal of Biological Chemistry最新文献

{"title":"C-terminal dimerization motifs control asynchronous chain elongation during modular polyketide biosynthesis.","authors":"Chengli Liu, Ryan C West, Muyuan Chen, Whitaker Cohn, George Wang, Selena Kim, Aryan M Mandot, Kym F Faull, Dillon P Cogan","doi":"10.1016/j.jbc.2026.113119","DOIUrl":"https://doi.org/10.1016/j.jbc.2026.113119","url":null,"abstract":"<p><p>The rifamycin synthetase (RIFS) from the bacterium Amycolatopsis mediterranei is a homodimeric assembly line that catalyzes 40+ chemical reactions to generate a complex precursor of the antitubercular drug rifampicin. It consists of an N-terminal substrate loading module (LM) followed by a decamodular polyketide synthase (PKS). While the catalytic functions are known for each domain of RIFS, how these activities are spatially and temporally coordinated during polyketide assembly remains incompletely defined. Here, we address this problem with thiol-selective crosslinking to understand the basis for conformational asymmetry during polyketide chain elongation. Our data suggest that C-terminal dimerization motifs-which are ubiquitous in bacterial PKS assembly lines-force their adjacent substrate carrier protein (CP) domains to co-migrate between two equivalent ketosynthase (KS) active site chambers. Cryogenic electron microscopy analysis of the first PKS module of RIFS (M1) further underscored this observation while revealing its unique architecture. Single-turnover kinetic analysis indicated that although changes to the C-terminus that reduced CP dimerization supported 2-fold greater KS:CP interactions, they were insufficient to overcome sub-stoichiometric product accumulation on the homodimeric protein. Our findings illuminate factors underlying asymmetry during polyketide antibiotic biosynthesis and should be instructive to future megasynth(et)ase engineers.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"113119"},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cryptic-site ligand stabilizes a non-canonical interface and blocks membrane insertion of the chloride intracellular channel CLIC1.","authors":"Shobhan Kuila, Archita Ghoshal, Sibasis Sahoo, Muthusankar Aathi, Mohd Azeem Khan, Love Panchariya, Kirti Shila Sonkar, Wajahat Ali Khan, Jaswanth Raj Pandiramesh, Anmol Chandele, Arockiasamy Arulandu","doi":"10.1016/j.jbc.2026.113113","DOIUrl":"https://doi.org/10.1016/j.jbc.2026.113113","url":null,"abstract":"<p><p>Human chloride intracellular channel 1 (HsCLIC1) is a dimorphic protein that exists in both soluble enzymatic and membrane-integrated ion channel forms. It is overexpressed in many cancers, yet developing specific inhibitors has been challenging, leaving CLIC proteins largely untargeted. Here, we identified a non-canonical ligand binding site on the soluble enzymatic form of HsCLIC1 and demonstrate that it is druggable with the small molecule inhibitor NSC602247. This cryptic site was discovered using multi-solvent molecular dynamics simulations followed by virtual screening and molecular docking. Using surface plasmon resonance and microscale thermophoresis, we show that NSC602247 binds to HsCLIC1 with micromolar affinity (∼6 μM) and inhibits the proliferation of HT29 colorectal cancer cells. To understand the mechanism of inhibition, we determined the crystal structure of the HsCLIC1-NSC602247 complex. Mechanistically, NSC602247 binding induces oligomerization of soluble HsCLIC1 and reduces its membrane expression, as revealed using flow cytometry. Our data clearly indicate that NSC602247 inhibits HT29 growth by sequestering the protein in a soluble state, thereby blocking its membrane translocation. These findings validate a novel cryptic site on CLIC1 and present a new mechanistic paradigm for inhibiting its pathological function by preventing membrane insertion, offering a promising strategy for targeted therapeutic development.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"113113"},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arylsulfatase L is a Golgi chondroitin sulfatase regulating skeletal development.","authors":"Marianna Maddaluno, Chiara De Leonibus, Eugenio Del Prete, Francesco Giuseppe Salierno, Daniela Intartaglia, Diego Carrella, Ivan Conte, Nicola Volpi, Carmine Settembre","doi":"10.1016/j.jbc.2026.113111","DOIUrl":"https://doi.org/10.1016/j.jbc.2026.113111","url":null,"abstract":"<p><p>Sulfatases are a family of enzymes that hydrolyze sulfate esters from various substrates. Defects, in sulfatase activity, are associated with various human diseases due to the accumulation of sulfated substrates. Deficiency in ARSL, a Golgi sulfatase, is associated with X-linked recessive chondrodysplasia punctata (CDPX), a disorder characterized by defects in cartilage and bone development. However, until now, ARSL function has remained unknown. In this study, we demonstrate that ARSL promotes 4-O-desulfation of Chondroitin Sulfate (CS) during proteoglycan biosynthesis. Chondrocytes lacking ARSL exhibit hypersulfated CS and altered responses to TGF-β stimulation. Loss of function of ARSL orthologous in medaka fish (Ol-Arsd) results in hyper-4-O-sulfated CS, skeletal malformations, and craniofacial defects that partly resemble the human CDPX phenotype. Our findings uncover a previously unrecognized step in glycosaminoglycan (GAG) maturation-Golgi-based desulfation-and reveal a new layer of regulatory control in skeletal development.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"113111"},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacillus cereus PelA_DA is a polysaccharide de-N-acetylase required for Pel-dependent biofilm formation.","authors":"Adithya S Subramanian, Francois Le Mauff, Elena N Kitova, Roland Pfoh, Mayura Panjalingam, Dung-Yeh Wu, Stephanie Gilbert, Zachary A Morrison, Christian A Jacobsen-Pérez, Erum Razvi, Mark Nitz, Jeroen Codée, John S Klassen, Donald C Sheppard, P Lynne Howell","doi":"10.1016/j.jbc.2026.113122","DOIUrl":"https://doi.org/10.1016/j.jbc.2026.113122","url":null,"abstract":"<p><p>Exopolysaccharides are key matrix determinants that provide structural integrity and regulate biomechanical properties of microbial biofilms. Biofilm exopolysaccharides often undergo modifications that determine their functional properties and localization. In B. cereus ATCC 10987, PelA_DA expressed from the pelDEA_DAFG operon is a putative deacetylase required for Pel-dependent biofilm formation. To understand the molecular basis of Pel deacetylation in B. cereus ATCC 10987, we determined the crystal structure of PelA_DA to 2.51 Å. PelA_DA adopts a distinct three-domain arrangement. We demonstrate in vitro that PelA_DA deacetylates α-1,4-linked GalNAc substrates in a length-dependent manner and that the N-terminal domain functions as a carbohydrate binding module (CBM) capable of binding both GalNAc and partially deacetylated oligosaccharides. We found that the CBM domain together with the carbohydrate esterase (CE) domain forms an elongated carbohydrate binding cleft and that each domain is the founding member of two new CAZy families, CBMxx and CExx, respectively. Further, in vivo mutagenesis demonstrated that the catalytic activity of PelA_DA is required for Pel biosynthesis in B. cereus ATCC 10987. Employing AlphaFold, we propose a model wherein the N-terminal transmembrane helix of PelA_DA interacts with PelG. This interaction positions the protein to accept the polymer for deacetylation as it emerges from the cytoplasmic membrane. The work presented herein offers insight into the role of PelA_DA in Pel biosynthesis and modification in B. cereus ATCC 10987.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"113122"},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Evaluation of TRPC6 Missense Variants in Cancer Patients via Molecular Docking Analysis Compared with Patch Clamp Electrophysiology.","authors":"Ying Wu, Xiaojing Sun, Joseph S Reddy, Pooja P Advani, Nicholas J Boddicker, James R Cerhan, Hector R Villarraga, Samuel J Asirvatham, Ru-Xing Wang, Hon-Chi Lee, Nadine Norton, Fernando B Zanchi, Tong Lu","doi":"10.1016/j.jbc.2026.113124","DOIUrl":"https://doi.org/10.1016/j.jbc.2026.113124","url":null,"abstract":"<p><p>Gain-of-function mutations in the transient receptor potential 6 (TRPC6) channel have been identified as risk factors for doxorubicin (DOX)-induced cardiomyopathy and heart failure. Functional characterization of TRPC6 missense variants is therefore important for cancer patients undergoing anthracycline therapy; however, conventional electrophysiological methods are labor-intensive and time-consuming. Here, we evaluated the functional responses of TRPC6 missense variants to 1-oleoyl-2-acetyl-sn-glycerol (OAG), a TRPC6 agonist, using molecular docking and patch-clamp recording. For the wild-type (WT) TRPC6 structure (PDB ID: 6UZ8), OAG exhibited a binding energy of -4.49 kcal/mol and a dissociation constant (Kd) of 0.511 mM. Twenty missense variants were identified from cancer patients, of which fifteen had resolvable structures. Among these, nine variants showed increased Kd values and six showed decreased Kd values relative to WT. Patch-clamp recordings demonstrated that WT and mutant channels were inactive at baseline but were activated by 50 μM OAG, except for two loss-of-function variants. Notably, all three variants identified in patients with heart failure exhibited loss-of-function properties in both electrophysiological and in silico analyses. Furthermore, 24-hour treatment with 0.5 μM DOX significantly potentiated OAG-induced channel activation in WT and gain-of-function variants, but not in loss-of-function variants. Importantly, our molecular docking and electrophysiological results were strongly correlated, with an 82% concordance rate, exceeding AlphaMissense predictions. These findings indicate that our computational analysis provides a rapid and reliable method for predicting the functional impact of TRPC6 missense variants, which may aid clinical decision-making in cancer patients receiving chemotherapy.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"113124"},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylation Marks Breast Cancer Metastasis: The Roles of m⁶A-Modified miRNAs and lncRNAs.","authors":"Brock A Humphries, Zhishan Wang, Chengfeng Yang","doi":"10.1016/j.jbc.2026.113127","DOIUrl":"https://doi.org/10.1016/j.jbc.2026.113127","url":null,"abstract":"<p><p>Breast cancer is the most commonly diagnosed cancer and a leading cause of death in women, with metastasis accounting for most of these fatalities. The mechanism of breast cancer metastasis has not been well understood. Recent research shows that chemical modifications added to RNA molecules after they are made, specifically the addition of a methyl group on the N⁶ position of an adenosine (N⁶-methyladenosine), play a crucial role in how cancer develops, adapts, and resists therapy. This review covers recent advances in understanding how these modifications regulate two major groups of regulatory RNAs, microRNAs and long noncoding RNAs. Our review highlights that methylation can alter the production, stability, and activity of these RNAs specifically in the context of breast cancer, influencing cell growth, migration, invasion, and resistance to chemotherapy, all of which are key processes in metastasis. We discuss how changes in RNA methylation, regulated by enzymes that add, remove, or recognize these marks, help breast cancer cells adapt to their environment, evade immune detection, and colonize new tissues. The evidence strongly suggests that RNA methylation and its control of regulatory RNAs drives breast cancer progression and survival. Targeting these pathways may allow for more precise diagnostic tests, risk prediction, and development of new treatments. However, further research is required to unravel how these modifications interact with other cellular processes and to translate these findings into effective therapies.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"113127"},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geranylgeraniol promotes osteoblast differentiation and inhibits osteoclastogenesis through MAPK and nuclear receptor signaling.","authors":"Mineko Tomomura, Takao Tsukahara, Ryuichiro Suzuki, Hiroshi Sakagami, Kenjiro Bandow, Akito Tomomura","doi":"10.1016/j.jbc.2026.113108","DOIUrl":"https://doi.org/10.1016/j.jbc.2026.113108","url":null,"abstract":"<p><p>Bone is regulated in a coordinated manner through the catabolic action of osteoclasts and the anabolic function of osteoblasts. Geranylgeraniol (GGOH) is a diterpenoid alcohol found in plant oils and is an intermediate in the mevalonate pathway. GGOH suppressed receptor activator of NF-κB ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive multinuclear osteoclast formation via downregulation of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) expression. Among the RANKL-activated mitogen-activated protein kinases (MAPKs) in bone marrow cells, phosphorylation of c-Jun amino-terminal kinase (JNK) was significantly suppressed following GGOH treatment. In contrast, GGOH stimulates alkaline phosphatase (ALP) activity and mineralization in calvarial osteoblasts. GGOH increased the expression of osteoblast biomarkers such as collagen type 1 and ALP, and osteogenic genes, such as Msx2, Runx2, and Smad. MAPK signaling pathway (JNK, p38, ERK) and NF-κB were augmented by GGOH. GGOH-induced ALP expression was suppressed by a farnesoid X receptor (FXR) antagonist, whereas FXR agonist increased ALP activity in osteoblasts. In contrast, the suppressive effect of GGOH on RANKL-induced TRAP activity in osteoclasts was attenuated by liver X receptor (LXR) and FXR antagonists, and these agonists mimicked the effect of GGOH. GGOH restored bisphosphonate-suppressed osteoblast differentiation. GGOH also showed protective effects against lipopolysaccharide (LPS)-induced bone resorption both in vitro and in vivo. Furthermore, GGOH treatment improved bone loss in ovariectomized mice. These results suggest that GGOH is a potent osteogenic and osteoprotective factor that promotes osteoblast differentiation and suppresses osteoclast differentiation, at least through nuclear receptor activation.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"113108"},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A thiadiazolylidene-morpholine compound inhibits Pseudomonas aeruginosa by destabilising the thiamine monophosphate kinase thiL.","authors":"Yingying Li, Jianqing Lin, Zara Chung, Benny Ken Yee Yeo, Julien Lescar, Kevin Pethe","doi":"10.1016/j.jbc.2026.113112","DOIUrl":"https://doi.org/10.1016/j.jbc.2026.113112","url":null,"abstract":"<p><p>Pseudomonas aeruginosa, an opportunistic Gram-negative pathogen, poses a growing threat in healthcare-associated infections. Its intrinsic resistance and acquisition of carbapenemases have driven widespread multidrug resistance and severely limited treatment options. P. aeruginosa causes life-threatening infections including ventilator-associated pneumonia, bloodstream infections, complicated urinary tract infections, and chronic lung disease in cystic fibrosis. We identified and validated thiL, encoding thiamine monophosphate kinase, as a critical metabolic vulnerability and promising antibacterial target. ThiL deletion abolished virulence in murine lung and wound models and rendered bacteria incapable of survival without a supra-physiological level of thiamine pyrophosphate (TPP). A screen of 1,231 kinase inhibitors identified VP3.15 as the first specific ThiL inhibitor with antibacterial potency. Mechanistic studies showed VP3.15 destabilizes ThiL, promoting protein unfolding and functional loss. These results establish ThiL as a druggable target and highlight metabolic dependencies as a therapeutic opportunity against multidrug-resistant P. aeruginosa.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"113112"},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel autopolysialylation activity of the ganglioside sialyltransferase ST8Sia5 regulates its secretion and enzyme activity.","authors":"Fumiya Sakamoto, Rina Hatanaka, Masaya Hane, Di Wu, Ken Kitajima, Chihiro Sato","doi":"10.1016/j.jbc.2026.113106","DOIUrl":"https://doi.org/10.1016/j.jbc.2026.113106","url":null,"abstract":"<p><p>Polysialic acid (polySia) is a linear polymer of sialic acid, which usually modifies N-glycans on the neural cell adhesion molecule (NCAM) mostly in the brain and is involved in the development of brain. PolySia is also associated with several diseases, including mental disorders and cancers. ST8Sia2 and ST8Sia4 are believed to be the only polysialyltransferases that synthesize polySia on NCAM (NCAM polysialylation). These enzymes are also autopolysialylated. In this study, we first found that ST8Sia5L, a ganglioside-specific sialyltransferase, has an activity to synthesize polysialic acid on ST8Sia5 itself, but does not exhibit the NCAM polysialylation activity. Notably, in silico and biochemical analyses revealed that ST8Sia5L contains a new polysialic acid trapping motif (PSTM) that is essential for polySia elongation, instead of the conventional polysialyltransferase domain (PSTD) found in ST8Sia2 and ST8Sia4. We also found that autopolysialylated ST8Sia5L is secreted from the cells. To identify the autopolysialylation sites involved in secretion, we performed N-glycosylation site disruption experiments, and found that N92 and N277 in the five N-glycosylation sites are important for this phenomenon. Furthermore, the inhibitor experiments showed that certain metalloprotease(s), but not exosomal pathways, are involved in the secretion. Notably, the secreted autopolysialylated enzyme showed no ganglioside-sialylation activity; however, the activity was recovered when polySia was removed by sialidase treatment. Overall, we show that autopolysialylation of ST8Sia5L regulates both its secretion and the conventional sialyltransferase activity.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"113106"},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An intricate functional relationship between NuA4 and Sfp1 regulates ribosome biogenesis in response to nutrient availability.","authors":"Ke Xu, Stéphanie Bianco, Charles Joly Beauparlant, Valérie Côté, Lara Herrmann, Arnaud Droit, Michael Downey, Amine Nourani, Jacques Côté","doi":"10.1016/j.jbc.2026.113107","DOIUrl":"https://doi.org/10.1016/j.jbc.2026.113107","url":null,"abstract":"<p><p>Ribosome biogenesis is a crucial process requiring enormous transcriptional output. In budding yeast, the expression of 138 ribosomal protein (RP) genes and over 200 ribosome biogenesis (RiBi) genes is regulated by an intricate network of factors, including the nutrient-sensitive transcription activator Sfp1 and the NuA4 coactivator/acetyltransferase complex. Nutrient starvation or inhibition of TORC1 by rapamycin leads to repression of RP and RiBi genes, in part through blocking Sfp1 nuclear localization and NuA4-dependent chromatin acetylation. Here, we demonstrate that Sfp1 physically interacts with NuA4 in a TORC1-dependent manner. Our results indicate that Sfp1, along with NuA4, regulate the transcription of RiBi and RP genes via distinct mechanisms depending on promoter architectures. Sfp1 promotes histone acetylation at the promoters without affecting NuA4 recruitment. In contrast, NuA4 does impact Sfp1 binding but specifically at two classes of RP genes. Importantly, NuA4 acetylates Sfp1 at lysines 655 and 657, regulating its function. Cells expressing Sfp1 with acetyl-mimicking mutations exhibit increased expression of RiBi genes while RP genes remain stable. However, the same mutants lead to the loss of Sfp1 binding/activity at RiBi genes when cells are under non-optimal growth conditions. Mimicking constitutive acetylation of Sfp1 also limits the transcriptional burst of RP genes upon addition of glucose. Altogether, these results draw an intricate functional relationship between Sfp1 and NuA4 to control ribosome biogenesis, fine-tuning transcription output in different growth conditions.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"113107"},"PeriodicalIF":4.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}