Molecular and Cellular Biology最新文献_第7页

Sumoylation is Largely Dispensable for Normal Growth but Facilitates Heat Tolerance in Yeast. sumo化在酵母的正常生长中是必不可少的，但它促进了酵母的耐热性。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 DOI: 10.1080/10985549.2023.2166320

Marjan Moallem, Akhi Akhter, Giovanni L Burke, John Babu, Benjamin G Bergey, J Bryan McNeil, Mohammad S Baig, Emanuel Rosonina

{"title":"Sumoylation is Largely Dispensable for Normal Growth but Facilitates Heat Tolerance in Yeast.","authors":"Marjan Moallem, Akhi Akhter, Giovanni L Burke, John Babu, Benjamin G Bergey, J Bryan McNeil, Mohammad S Baig, Emanuel Rosonina","doi":"10.1080/10985549.2023.2166320","DOIUrl":"https://doi.org/10.1080/10985549.2023.2166320","url":null,"abstract":"Numerous proteins are sumoylated in normally growing yeast and SUMO conjugation levels rise upon exposure to several stress conditions. We observe high levels of sumoylation also during early exponential growth and when nutrient-rich medium is used. However, we find that reduced sumoylation (∼75% less than normal) is remarkably well-tolerated, with no apparent growth defects under nonstress conditions or under osmotic, oxidative, or ethanol stresses. In contrast, strains with reduced activity of Ubc9, the sole SUMO conjugase, are temperature-sensitive, implicating sumoylation in the heat stress response, specifically. Aligned with this, a mild heat shock triggers increased sumoylation which requires functional levels of Ubc9, but likely also depends on decreased desumoylation, since heat shock reduces protein levels of Ulp1, the major SUMO protease. Furthermore, we find that a ubc9 mutant strain with only ∼5% of normal sumoylation levels shows a modest growth defect, has abnormal genomic distribution of RNA polymerase II (RNAPII), and displays a greatly expanded redistribution of RNAPII after heat shock. Together, our data implies that SUMO conjugations are largely dispensable under normal conditions, but a threshold level of Ubc9 activity is needed to maintain transcriptional control and to modulate the redistribution of RNAPII and promote survival when temperatures rise.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"43 1","pages":"64-84"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5a/58/TMCB_43_2166320.PMC9936996.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9176401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Exosome-transmitted circIFNGR2 Modulates Ovarian Cancer Metastasis via miR-378/ST5 Axis. 外泌体传递的circIFNGR2通过miR-378/ST5轴调节卵巢癌转移

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 Epub Date: 2023-01-26 DOI: 10.1080/10985549.2022.2160605

Xiaoping Chen, Xinping Ren, Jiaoting E, Yaqi Zhou, Rongfang Bian

{"title":"Exosome-transmitted circIFNGR2 Modulates Ovarian Cancer Metastasis via miR-378/ST5 Axis.","authors":"Xiaoping Chen, Xinping Ren, Jiaoting E, Yaqi Zhou, Rongfang Bian","doi":"10.1080/10985549.2022.2160605","DOIUrl":"10.1080/10985549.2022.2160605","url":null,"abstract":"Cancer-associated fibroblasts (CAFs)-derived exosomes have emerged as a key driver of ovarian cancer (OVCA) tumor progression. The mechanisms behind the specific circular RNA (circRNA) activity encapsulated by CAF-generated exosomes (CAF-exo) requires to be elucidated. Herein, this study selected specific circRNA (hsa_circIFNGR2) molecules and aimed to clarify novel function of CAF-derived exosomal circIFNGR2 on growth, and metastasis of OVCA cells. In this study, we clarified that the exosomes of CAFs originating from human ovarian cancer hindered tumor cell proliferation, metastasis and EMT in vitro. Interestingly, CAFs directly transferred exosomes into OVCA cells to enrich intracellular circIFNGR2 levels. Biologically, activation of exosomal circIFNGR2 blocked cell proliferation, metastasis and EMT. Mechanistically, enhanced circIFNGR2 activated the miR-378/ST5 axis and directly inhibited the malignant evolution of tumor cells. Furthermore, rescue experiments evidenced that circIFNGR2 and ST5 were two essential participants in OVCA, concretely manifested in the co-culture of OVCA cells with exosomes that reversed the effects of intracellular circIFNGR2 and ST5 depletion. Finally, we observed that CAF-exo treatment hindered tumor growth and increased the size and number of metastatic nodules in mice. Our study revealed a previously unknown regulatory pathway whereby CAFs-derived exosomes delivered circIFNGR2 and inhibited the malignant progression of OVCA by circIFNGR2/miR-378/ST5 axis.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"43 1","pages":"22-42"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9937009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9120083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CircTTLL13 Promotes TMZ Resistance in Glioma via Modulating OLR1-Mediated Activation of the Wnt/β-Catenin Pathway. CircTTLL13 通过调节 OLR1 介导的 Wnt/β-Catenin 通路激活促进胶质瘤的 TMZ 抗性

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 Epub Date: 2023-07-10 DOI: 10.1080/10985549.2023.2210032

Jun Li, Junfeng Ma, Shan Huang, Jun Li, Liang Zhou, Jiahua Sun, Lin Chen

{"title":"CircTTLL13 Promotes TMZ Resistance in Glioma via Modulating OLR1-Mediated Activation of the Wnt/β-Catenin Pathway.","authors":"Jun Li, Junfeng Ma, Shan Huang, Jun Li, Liang Zhou, Jiahua Sun, Lin Chen","doi":"10.1080/10985549.2023.2210032","DOIUrl":"10.1080/10985549.2023.2210032","url":null,"abstract":"Glioma, originating from neuroglial progenitor cells, is a type of intrinsic brain tumor with poor prognosis. temozolomide (TMZ) is the first-line chemotherapeutic agent for glioma. Exploring the mechanisms of circTTLL13 underlying TMZ resistance in glioma is of great significance to improve glioma treatment. Bioinformatics was adopted to identify target genes. The circular structure of circTTLL13 and its high expression in glioma cells were disclosed by quantitative real time-PCR (qRT-PCR) and PCR-agarose gel electrophoresis. Functional experiments proved that oxidized LDL receptor 1 (OLR1) promotes TMZ resistance of glioma cells. CircTTLL13 enhances TMZ resistance of glioma cells via modulating OLR1. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), RNA pulldown, mRNA stability, N6-methyladenosine (m6A) dot blot and RNA total m6A quantification assays were implemented, indicating that circTTLL13 stabilizes OLR1 mRNA via recruiting YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) and promotes m6A methylation of OLR1 pre-mRNA through recruiting methyltransferase-like 3 (METTL3). TOP/FOP-flash reporter assay and western blot verified that circTTLL13 activates Wnt/β-catenin signaling pathway by regulating OLR1. CircTTLL13 promotes TMZ resistance in glioma through regulating OLR1-mediated Wnt/β-catenin pathway activation. This study offers an insight into the efficacy improvement of TMZ for glioma treatment.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"43 7","pages":"354-369"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9809223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EPRS1 Controls the TGF-β Signaling Pathway via Interaction with TβRI in Hepatic Stellate Cell. EPRS1通过与TβRI相互作用调控肝星状细胞TGF-β信号通路。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 DOI: 10.1080/10985549.2023.2205344

Ina Yoon, Ji Ae Song, Ji Hun Suh, Sulhee Kim, Jonghyeon Son, Jong Hyun Kim, Song Yee Jang, Kwang Yeon Hwang, Myung Hee Kim, Sunghoon Kim

{"title":"EPRS1 Controls the TGF-β Signaling Pathway via Interaction with TβRI in Hepatic Stellate Cell.","authors":"Ina Yoon, Ji Ae Song, Ji Hun Suh, Sulhee Kim, Jonghyeon Son, Jong Hyun Kim, Song Yee Jang, Kwang Yeon Hwang, Myung Hee Kim, Sunghoon Kim","doi":"10.1080/10985549.2023.2205344","DOIUrl":"https://doi.org/10.1080/10985549.2023.2205344","url":null,"abstract":"Glutamyl-prolyl-tRNA synthetase 1 (EPRS1) is known to associated with fibrosis through its catalytic activity to produce prolyl-tRNA. Although its catalytic inhibitor halofuginone (HF) has been known to inhibit the TGF-β pathway as well as to reduce prolyl-tRNA production for the control of fibrosis, the underlying mechanism how EPRS1 regulates the TGF-β pathway was not fully understood. Here, we show a noncatalytic function of EPRS1 in controlling the TGF-β pathway and hepatic stellate cell activation via its interaction with TGF-β receptor I (TβRI). Upon stimulation with TGF-β, EPRS1 is phosphorylated by TGF-β-activated kinase 1 (TAK1), leading to its dissociation from the multi-tRNA synthetase complex and subsequent binding with TβRI. This interaction increases the association of TβRI with SMAD2/3 while decreases that of TβRI with SMAD7. Accordingly, EPRS1 stabilizes TβRI by preventing the ubiquitin-mediated degradation of TβRI. HF disrupts the interaction between EPRS1 and TβRI, and reduces TβRI protein levels, leading to inhibition of the TGF-β pathway. In conclusion, this work suggests the novel function of EPRS1 involved in the development of fibrosis by regulating the TGF-β pathway and the antifibrotic effects of HF by controlling both of EPRS1 functions.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"43 5","pages":"223-240"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/de/TMCB_43_2205344.PMC10184599.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

microRNA-130b May Induce Cerebral Vasospasm after Subarachnoid Hemorrhage via Modulating Kruppel-like Factor 4. microRNA-130b可能通过调节kruppel样因子4诱导蛛网膜下腔出血后脑血管痉挛。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 DOI: 10.1080/10985549.2023.2210030

Zewei Huang, Jiliang Hu, Jiongfu Xu, Hao Wang, Limeng Dai

{"title":"microRNA-130b May Induce Cerebral Vasospasm after Subarachnoid Hemorrhage via Modulating Kruppel-like Factor 4.","authors":"Zewei Huang, Jiliang Hu, Jiongfu Xu, Hao Wang, Limeng Dai","doi":"10.1080/10985549.2023.2210030","DOIUrl":"https://doi.org/10.1080/10985549.2023.2210030","url":null,"abstract":"Recently, the diverse functions of microRNAs (miRNAs) in brain diseases have been demonstrated. We intended to uncover the functional role of microRNA-130b (miR-130b) in cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH). SAH was induced by injecting the autologous blood into the cisterna magna of Sprague Dawley rats. The cerebral vascular smooth muscle cells (cVSMCs) were extracted for in vitro experimentation. In vitro and in vivo assays were implemented with transfection of miR-130b mimic/inhibitor, sh-Kruppel-like factor 4 (KLF4), oe-KLF4 plasmids or p38/MAPK signaling pathway agonist (anisomycin), respectively, to elaborate the role of miR-130b in CVS following SAH. Elevated miR-130b and reduced KLF4 were found in SAH patients and rat models of SAH. KLF4 was the target gene of miR-130b. miR-130b promoted the proliferation and migration of cVSMCs through the Inhibition of KLF4. Besides, KLF4 inhibited the proliferation and migration of cVSMCs through blockage of the p38/MAPK pathway. Furthermore, in vivo assay confirmed the inhibitory effect of decreased miR-130b in CVS following SAH. In conclusion, miR-130b may activate the p38/MAPK signaling pathway through targeted inhibition of KLF4, thereby contributing to some extent to the development of cerebral vasospasm after SAH.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"43 7","pages":"301-316"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/98/cc/TMCB_43_2210030.PMC10348024.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9835351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Receptor Recycling by Retromer. Retromer 的受体再循环。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 Epub Date: 2023-06-23 DOI: 10.1080/10985549.2023.2222053

Julian M Carosi, Donna Denton, Sharad Kumar, Timothy J Sargeant

{"title":"Receptor Recycling by Retromer.","authors":"Julian M Carosi, Donna Denton, Sharad Kumar, Timothy J Sargeant","doi":"10.1080/10985549.2023.2222053","DOIUrl":"10.1080/10985549.2023.2222053","url":null,"abstract":"The highly conserved retromer complex controls the fate of hundreds of receptors that pass through the endolysosomal system and is a central regulatory node for diverse metabolic programs. More than 20 years ago, retromer was discovered as an essential regulator of endosome-to-Golgi transport in yeast; since then, significant progress has been made to characterize how metazoan retromer components assemble to enable its engagement with endosomal membranes, where it sorts cargo receptors from endosomes to the trans-Golgi network or plasma membrane through recognition of sorting motifs in their cytoplasmic tails. In this review, we examine retromer regulation by exploring its assembled structure with an emphasis on how a range of adaptor proteins shape the process of receptor trafficking. Specifically, we focus on how retromer is recruited to endosomes, selects cargoes, and generates tubulovesicular carriers that deliver cargoes to target membranes. We also examine how cells adapt to distinct metabolic states by coordinating retromer expression and function. We contrast similarities and differences between retromer and its related complexes: retriever and commander/CCC, as well as their interplay in receptor trafficking. We elucidate how loss of retromer regulation is central to the pathology of various neurogenerative and metabolic diseases, as well as microbial infections, and highlight both opportunities and cautions for therapeutics that target retromer. Finally, with a focus on understanding the mechanisms that govern retromer regulation, we outline new directions for the field moving forward.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"43 7","pages":"317-334"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9799013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DNA Damage-Induced, S-Phase Specific Phosphorylation of Orc6 is Critical for the Maintenance of Genome Stability. DNA 损伤诱导的 Orc6 S 期特异性磷酸化对维持基因组稳定性至关重要

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 Epub Date: 2023-04-25 DOI: 10.1080/10985549.2023.2196204

Yo-Chuen Lin, Dazhen Liu, Arindam Chakraborty, Virgilia Macias, Eileen Brister, Jay Sonalkar, Linyuan Shen, Jaba Mitra, Taekjip Ha, Andre Kajdacsy-Balla, Kannanganattu V Prasanth, Supriya G Prasanth

{"title":"DNA Damage-Induced, S-Phase Specific Phosphorylation of Orc6 is Critical for the Maintenance of Genome Stability.","authors":"Yo-Chuen Lin, Dazhen Liu, Arindam Chakraborty, Virgilia Macias, Eileen Brister, Jay Sonalkar, Linyuan Shen, Jaba Mitra, Taekjip Ha, Andre Kajdacsy-Balla, Kannanganattu V Prasanth, Supriya G Prasanth","doi":"10.1080/10985549.2023.2196204","DOIUrl":"10.1080/10985549.2023.2196204","url":null,"abstract":"The smallest subunit of the human Origin Recognition Complex, hOrc6, is required for DNA replication progression and plays an important role in mismatch repair (MMR) during S-phase. However, the molecular details of how hOrc6 regulates DNA replication and DNA damage response remain to be elucidated. Orc6 levels are elevated upon specific types of genotoxic stress, and it is phosphorylated at Thr229, predominantly during S-phase, in response to oxidative stress. Many repair pathways, including MMR, mediate oxidative DNA damage repair. Defects in MMR are linked to Lynch syndrome, predisposing patients to many cancers, including colorectal cancer. Orc6 levels are known to be elevated in colorectal cancers. Interestingly, tumor cells show reduced hOrc6-Thr229 phosphorylation compared to adjacent normal mucosa. Further, elevated expression of wild-type and the phospho-dead forms of Orc6 results in increased tumorigenicity, implying that in the absence of this \"checkpoint\" signal, cells proliferate unabated. Based on these results, we propose that DNA-damage-induced hOrc6-pThr229 phosphorylation during S-phase facilitates ATR signaling in the S-phase, halts fork progression, and enables assembly of repair factors to mediate efficient repair to prevent tumorigenesis. Our study provides novel insights into how hOrc6 regulates genome stability.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"43 4","pages":"143-156"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10153009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9827625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcription-Driven Translocation of Cohesive and Non-Cohesive Cohesin In Vivo. 转录驱动的体内黏连蛋白和非黏连蛋白的转运

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 Epub Date: 2023-05-13 DOI: 10.1080/10985549.2023.2199660

Melinda S Borrie, Paul M Kraycer, Marc R Gartenberg

{"title":"Transcription-Driven Translocation of Cohesive and Non-Cohesive Cohesin In Vivo.","authors":"Melinda S Borrie, Paul M Kraycer, Marc R Gartenberg","doi":"10.1080/10985549.2023.2199660","DOIUrl":"10.1080/10985549.2023.2199660","url":null,"abstract":"Cohesin is a central architectural element of chromosomes that regulates numerous DNA-based events. The complex holds sister chromatids together until anaphase onset and organizes individual chromosomal DNAs into loops and self-associating domains. Purified cohesin diffuses along DNA in an ATP-independent manner but can be propelled by transcribing RNA polymerase. In conjunction with a cofactor, the complex also extrudes DNA loops in an ATP-dependent manner. In this study we examine transcription-driven translocation of cohesin under various conditions in yeast. To this end, obstacles of increasing size were tethered to DNA to act as roadblocks to complexes mobilized by an inducible gene. The obstacles were built from a GFP-lacI core fused to one or more mCherries. A chimera with four mCherries blocked cohesin passage in late G1. During M phase, the threshold barrier depended on the state of cohesion: non-cohesive complexes were also blocked by four mCherries whereas cohesive complexes were blocked by as few as three mCherries. Furthermore cohesive complexes that were stalled at obstacles, in turn, blocked the passage of non-cohesive complexes. That synthetic barriers capture mobilized cohesin demonstrates that transcription-driven complexes translocate processively in vivo. Together, this study reveals unexplored limitations to cohesin movement on chromosomes.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"43 6","pages":"254-268"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/94/10/TMCB_43_2199660.PMC10251789.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10239775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Scaffold Protein KATNIP Enhances CILK1 Control of Primary Cilia. 支架蛋白KATNIP增强原发性纤毛的CILK1控制。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 Epub Date: 2023-09-04 DOI: 10.1080/10985549.2023.2246870

Jacob S Turner, Ellie A McCabe, Kevin W Kuang, Casey D Gailey, David L Brautigan, Ana Limerick, Elena X Wang, Zheng Fu

{"title":"The Scaffold Protein KATNIP Enhances CILK1 Control of Primary Cilia.","authors":"Jacob S Turner, Ellie A McCabe, Kevin W Kuang, Casey D Gailey, David L Brautigan, Ana Limerick, Elena X Wang, Zheng Fu","doi":"10.1080/10985549.2023.2246870","DOIUrl":"10.1080/10985549.2023.2246870","url":null,"abstract":"The primary cilium functions as a cellular sensory organelle and signaling antenna that detects and transduces extracellular signals. Mutations in the human gene CILK1 (ciliogenesis associated kinase 1) cause abnormal cilia elongation and faulty Hedgehog signaling, associated with developmental disorders and epilepsy. CILK1 is a protein kinase that requires dual phosphorylation of its TDY motif for activation and its extended C-terminal intrinsically disordered region (IDR) mediates targeting to the basal body and substrate recognition. Proteomics previously identified katanin-interacting protein (KATNIP), also known as KIAA0556, as a CILK1 interacting partner. In this study we discovered that CILK1 colocalizes with KATNIP at the basal body and the CILK1 IDR is sufficient to mediate binding to KATNIP. Deletion analysis of KATNIP shows one of three domains of unknown function (DUF) is required for association with CILK1. KATNIP binding with CILK1 drastically elevated CILK1 protein levels and TDY phosphorylation in cells. This resulted in a profound increase in phosphorylation of known CILK1 substrates and suppression of cilia length. Thus, KATNIP functions as a regulatory subunit of CILK1 that potentiates its actions. This advances our understanding of the molecular basis of control of primary cilia.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"43 9","pages":"472-480"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10512882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10297389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RNA Polymerase II Dependent Crosstalk between H4K16 Deacetylation and H3K56 Acetylation Promotes Transcription of Constitutively Expressed Genes. H4K16去乙酰化和H3K56乙酰化之间的RNA聚合酶II依赖性串扰促进组成表达基因的转录。

IF 4.3 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 Epub Date: 2023-11-17 DOI: 10.1080/10985549.2023.2270912

Preeti Khan, Priyabrata Singha, Ronita Nag Chaudhuri

{"title":"RNA Polymerase II Dependent Crosstalk between H4K16 Deacetylation and H3K56 Acetylation Promotes Transcription of Constitutively Expressed Genes.","authors":"Preeti Khan, Priyabrata Singha, Ronita Nag Chaudhuri","doi":"10.1080/10985549.2023.2270912","DOIUrl":"10.1080/10985549.2023.2270912","url":null,"abstract":"Nucleosome dynamics in the coding region of a transcriptionally active locus is critical for understanding how RNA polymerase II progresses through the gene body. Histone acetylation and deacetylation critically influence nucleosome accessibility during DNA metabolic processes like transcription. Effect of such histone modifications is context and residue dependent. Rather than effect of individual histone residues, the network of modifications of several histone residues in combination generates a chromatin landscape that is conducive for transcription. Here we show that in Saccharomyces cerevisiae, crosstalk between deacetylation of the H4 N-terminal tail residue H4K16 and acetylation of the H3 core domain residue H3K56, promotes RNA polymerase II progression through the gene body. Results indicate that deacetylation of H4K16 precedes and in turn induces H3K56 acetylation. Effectively, recruitment of Rtt109, the HAT responsible for H3K56 acetylation is essentially dependent on H4K16 deacetylation. In Hos2 deletion strains, where H4K16 deacetylation is abolished, both H3K56 acetylation and RNA polymerase II recruitment gets significantly impaired. Notably, H4K16 deacetylation and H3K56 acetylation are found to be essentially dependent on active transcription. In summary, H4K16 deacetylation promotes H3K56 acetylation and the two modifications together work towards successful functioning of RNA polymerase II during active transcription.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"596-610"},"PeriodicalIF":4.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0