Molecular and Cellular Biology最新文献_第8页

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

Correction. 修正。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 Epub Date: 2023-11-17 DOI: 10.1080/10985549.2023.2277100

引用次数: 0

Methyltransferase Inhibition Enables Tgfβ Driven Induction of CDKN2A and B in Cancer Cells. 甲基转移酶抑制可使 Tgfβ 在癌细胞中诱导 CDKN2A 和 B。

IF 5.3 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 DOI: 10.1080/10985549.2023.2186074

Yen-Ting Liu, Celeste Romero, Xue Xiao, Lei Guo, Xiaoyun Zhou, Mark A Applebaum, Lin Xu, Stephen X Skapek

{"title":"Methyltransferase Inhibition Enables Tgfβ Driven Induction of CDKN2A and B in Cancer Cells.","authors":"Yen-Ting Liu, Celeste Romero, Xue Xiao, Lei Guo, Xiaoyun Zhou, Mark A Applebaum, Lin Xu, Stephen X Skapek","doi":"10.1080/10985549.2023.2186074","DOIUrl":"10.1080/10985549.2023.2186074","url":null,"abstract":"CDKN2A/B deletion or silencing is common across human cancer, reinforcing the general importance of bypassing its tumor suppression in cancer formation or progression. In rhabdomyosarcoma (RMS) and neuroblastoma, two common childhood cancers, the three CDKN2A/B transcripts are independently expressed to varying degrees, but one, ARF, is uniformly silenced. Although TGFβ induces certain CDKN2A/B transcripts in HeLa cells, it was unable to do so in five tested RMS lines unless the cells were pretreated with a broadly acting methyltransferase inhibitor, DZNep, or one targeting EZH2. CDKN2A/B induction by TGFβ correlated with de novo appearance of three H3K27Ac peaks within a 20 kb cis element ∼150 kb proximal to CDKN2A/B. Deleting that segment prevented their induction by TGFβ but not a basal increase driven by methyltransferase inhibition alone. Expression of two CDKN2A/B transcripts was enhanced by dCas9/CRISPR activation targeting either the relevant promoter or the 20 kb cis elements, and this \"precise\" manipulation diminished RMS cell propagation in vitro. Our findings show crosstalk between methyltransferase inhibition and TGFβ-dependent activation of a remote enhancer to reverse CDKN2A/B silencing. Though focused on CDKN2A/B here, such crosstalk may apply to other TGFβ-responsive genes and perhaps govern this signaling protein's complex effects promoting or blocking cancer.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"43 3","pages":"115-129"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10038032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9646911","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

Degradation of CDK9 by Ubiquitin E3 Ligase STUB1 Regulates P-TEFb Level and Its Functions for Global Target Gene Expression within Mammalian Cells. 泛素E3连接酶STUB1对CDK9的降解调节P-TEFb水平及其在哺乳动物细胞内全局靶基因表达的功能。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 Epub Date: 2023-08-11 DOI: 10.1080/10985549.2023.2239694

Subham Basu, Arijit Nandy, Avik Ghosh, Dheerendra Pratap Mall, Debabrata Biswas

{"title":"Degradation of CDK9 by Ubiquitin E3 Ligase STUB1 Regulates P-TEFb Level and Its Functions for Global Target Gene Expression within Mammalian Cells.","authors":"Subham Basu, Arijit Nandy, Avik Ghosh, Dheerendra Pratap Mall, Debabrata Biswas","doi":"10.1080/10985549.2023.2239694","DOIUrl":"10.1080/10985549.2023.2239694","url":null,"abstract":"Positive transcription elongation factor b (P-TEFb) regulates expression of diverse sets of genes within mammalian cells that have implications in several human disease pathogeneses. However, mechanisms of functional regulation of P-TEFb complex through regulation of its stability are poorly known. In this study, we show an important role of C-terminus of Hsc70-interacting protein (CHIP aka STUB1) in regulation of overall level of CDK9 and thus P-TEFb complex within mammalian cells. STUB1 acts as a ubiquitin E3 ligase for proteasomal degradation of CDK9 involving N-terminal lysine 3 (K3) residue. Whereas, overexpression of STUB1 enhances, its knockdown reduces overall CDK9 degradation kinetics within mammalian cells. Interestingly, owing to the same region of binding within CDK9, CyclinT1 protects CDK9 from STUB1-mediated degradation. Factors that cooperatively bind with CyclinT1 to form functional complex also protects CDK9 from degradation by STUB1. Knockdown of STUB1 enhances CDK9 expression and thus P-TEFb complex formation that leads to global increase in RNA polymerase II CTD phosphorylation and transcriptional activation of diverse P-TEFb target genes. Thus, we describe an important functional role of STUB1 in regulation of transcription through modulation of overall level of P-TEFb complex formation within mammalian cells.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"43 9","pages":"451-471"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10512928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10294787","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

Fission Yeast TORC1 Promotes Cell Proliferation through Sfp1, a Transcription Factor Involved in Ribosome Biogenesis. 裂殖酵母 TORC1 通过参与核糖体生物发生的转录因子 Sfp1 促进细胞增殖

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 Epub Date: 2023-12-20 DOI: 10.1080/10985549.2023.2282349

Yen Teng Tai, Tomoyuki Fukuda, Yuichi Morozumi, Hayato Hirai, Arisa H Oda, Yoshiaki Kamada, Yutaka Akikusa, Tomotake Kanki, Kunihiro Ohta, Kazuhiro Shiozaki

{"title":"Fission Yeast TORC1 Promotes Cell Proliferation through Sfp1, a Transcription Factor Involved in Ribosome Biogenesis.","authors":"Yen Teng Tai, Tomoyuki Fukuda, Yuichi Morozumi, Hayato Hirai, Arisa H Oda, Yoshiaki Kamada, Yutaka Akikusa, Tomotake Kanki, Kunihiro Ohta, Kazuhiro Shiozaki","doi":"10.1080/10985549.2023.2282349","DOIUrl":"10.1080/10985549.2023.2282349","url":null,"abstract":"Target of rapamycin complex 1 (TORC1) is activated in response to nutrient availability and growth factors, promoting cellular anabolism and proliferation. To explore the mechanism of TORC1-mediated proliferation control, we performed a genetic screen in fission yeast and identified Sfp1, a zinc-finger transcription factor, as a multicopy suppressor of temperature-sensitive TORC1 mutants. Our observations suggest that TORC1 phosphorylates Sfp1 and protects Sfp1 from proteasomal degradation. Transcription analysis revealed that Sfp1 positively regulates genes involved in ribosome production together with two additional transcription factors, Ifh1/Crf1 and Fhl1. Ifh1 physically interacts with Fhl1, and the nuclear localization of Ifh1 is regulated in response to nutrient levels in a manner dependent on TORC1 and Sfp1. Taken together, our data suggest that the transcriptional regulation of the genes involved in ribosome biosynthesis by Sfp1, Ifh1, and Fhl1 is one of the key pathways through which nutrient-activated TORC1 promotes cell proliferation.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"675-692"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487994","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

A PTP1B-Cdk3 Signaling Axis Promotes Cell Cycle Progression of Human Glioblastoma Cells through an Rb-E2F Dependent Pathway. PTP1B-Cdk3信号轴通过Rb-E2F依赖途径促进人胶质母细胞瘤细胞周期进程

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 Epub Date: 2023-12-20 DOI: 10.1080/10985549.2023.2273193

Olga Villamar-Cruz, Marco Antonio Loza-Mejía, Alonso Vivar-Sierra, Héctor Iván Saldivar-Cerón, Genaro Patiño-López, Jonadab Efraín Olguín, Luis Ignacio Terrazas, Leonel Armas-López, Federico Ávila-Moreno, Sayanti Saha, Jonathan Chernoff, Ignacio Camacho-Arroyo, Luis Enrique Arias-Romero

{"title":"A PTP1B-Cdk3 Signaling Axis Promotes Cell Cycle Progression of Human Glioblastoma Cells through an Rb-E2F Dependent Pathway.","authors":"Olga Villamar-Cruz, Marco Antonio Loza-Mejía, Alonso Vivar-Sierra, Héctor Iván Saldivar-Cerón, Genaro Patiño-López, Jonadab Efraín Olguín, Luis Ignacio Terrazas, Leonel Armas-López, Federico Ávila-Moreno, Sayanti Saha, Jonathan Chernoff, Ignacio Camacho-Arroyo, Luis Enrique Arias-Romero","doi":"10.1080/10985549.2023.2273193","DOIUrl":"10.1080/10985549.2023.2273193","url":null,"abstract":"PTP1B plays a key role in developing different types of cancer. However, the molecular mechanism underlying this effect is unclear. To identify molecular targets of PTP1B that mediate its role in tumorigenesis, we undertook a SILAC-based phosphoproteomic approach, which allowed us to identify Cdk3 as a novel PTP1B substrate. Substrate trapping experiments and docking studies revealed stable interactions between the PTP1B catalytic domain and Cdk3. In addition, we observed that PTP1B dephosphorylates Cdk3 at tyrosine residue 15 in vitro and interacts with it in human glioblastoma cells. Next, we found that pharmacological inhibition of PTP1B or its depletion with siRNA leads to cell cycle arrest with diminished activity of Cdk3, hypophosphorylation of Rb, and the downregulation of E2F target genes Cdk1, Cyclin A, and Cyclin E1. Finally, we observed that the expression of a constitutively active Cdk3 mutant bypasses the requirement of PTP1B for cell cycle progression and expression of E2F target genes. These data delineate a novel signaling pathway from PTP1B to Cdk3 required for efficient cell cycle progression in an Rb-E2F dependent manner in human GB cells.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"631-649"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138445468","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

Phosphorylation of the Myogenic Factor Myocyte Enhancer Factor-2 Impacts Myogenesis In Vivo. 肌生成因子-肌细胞增强因子-2的磷酸化影响体内肌生成。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2023-01-01 Epub Date: 2023-05-15 DOI: 10.1080/10985549.2023.2198167

Kumar Vishal, Elizabeth Barajas Alonso, Ashley A DeAguero, Jennifer A Waters, Maria B Chechenova, Richard M Cripps

{"title":"Phosphorylation of the Myogenic Factor Myocyte Enhancer Factor-2 Impacts Myogenesis In Vivo.","authors":"Kumar Vishal, Elizabeth Barajas Alonso, Ashley A DeAguero, Jennifer A Waters, Maria B Chechenova, Richard M Cripps","doi":"10.1080/10985549.2023.2198167","DOIUrl":"10.1080/10985549.2023.2198167","url":null,"abstract":"Activity of the myogenic regulatory protein myocyte enhancer factor-2 (MEF2) is modulated by post-translational modification. We investigated the in vivo phosphorylation of Drosophila MEF2, and identified serine 98 (S98) as a phosphorylated residue. Phospho-mimetic (S98E) and phospho-null (S98A) isoforms of MEF2 did not differ from wild-type in their activity in vitro, so we used CRISPR/Cas9 to generate an S98A allele of the endogenous gene. In mutant larvae we observed phenotypes characteristic of reduced MEF2 function, including reduced body wall muscle size and reduced expression of myofibrillar protein genes; conversely,S98A homozygotes showed enhanced MEF2 function through muscle differentiation within the adult myoblasts associated with the wing imaginal disc. In adults, S98A homozygotes were viable with normal mobility, yet showed patterning defects in muscles that were enhanced when the S98A allele was combined with a Mef2 null allele. Overall our data indicate that blocking MEF2 S98 phosphorylation in myoblasts enhances its myogenic capability, whereas blocking S98 phosphorylation in differentiating muscles attenuates MEF2 function. Our studies are among the first to assess the functional significance of MEF2 phosphorylation sites in the intact animal, and suggest that the same modification can have profoundly different effects upon MEF2 function depending upon the developmental context.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"43 6","pages":"241-253"},"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/7d/ed/TMCB_43_2198167.PMC10251773.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10176914","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