Molecular and Cellular Biology最新文献_第3页

A Genome Wide CRISPR Screen Reveals That HOXA9 Promotes Enzalutamide Resistance in Prostate Cancer. 全基因组 CRISPR 筛选揭示 HOXA9 可促进前列腺癌的恩杂鲁胺抗性

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-09-20 DOI: 10.1080/10985549.2024.2401465

Michael V Roes, Frederick A Dick

{"title":"A Genome Wide CRISPR Screen Reveals That HOXA9 Promotes Enzalutamide Resistance in Prostate Cancer.","authors":"Michael V Roes, Frederick A Dick","doi":"10.1080/10985549.2024.2401465","DOIUrl":"10.1080/10985549.2024.2401465","url":null,"abstract":"Androgen receptor inhibitors are commonly used for prostate cancer treatment, but acquired resistance is a significant problem. Codeletion of RB and p53 is common in castration resistant prostate cancers, however they are difficult to target pharmacologically. To comprehensively identify gene loss events that contribute to enzalutamide response, we performed a genome-wide CRISPR knockout screen in LNCaP prostate cancer cells. This revealed novel genes implicated in resistance that are largely unstudied. Gene loss events that confer enzalutamide sensitivity are enriched for GSEA categories related to stem cell and epigenetic regulation. We investigated the myeloid lineage stem cell factor HOXA9 as a candidate gene whose loss promotes sensitivity to enzalutamide. Cancer genomic data reveals that HOXA9 overexpression correlates with poor prognosis and characteristics of advanced prostate cancer. In cell culture, HOXA9 depletion sensitizes cells to enzalutamide, whereas overexpression drives enzalutamide resistance. Combination of the HOXA9 inhibitor DB818 with enzalutamide demonstrates synergy. This demonstrates the utility of our CRISPR screen data in discovering new approaches for treating enzalutamide resistant prostate cancer.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"529-542"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291286","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

Discovery of Transcription Factors Involved in the Maintenance of Resident Vascular Endothelial Stem Cell Properties. 发现参与维持驻留血管内皮干细胞特性的转录因子。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-01-29 DOI: 10.1080/10985549.2023.2297997

Hirotaka Konishi, Fitriana N Rahmawati, Naoki Okamoto, Keigo Akuta, Koichi Inukai, Weizhen Jia, Fumitaka Muramatsu, Nobuyuki Takakura

{"title":"Discovery of Transcription Factors Involved in the Maintenance of Resident Vascular Endothelial Stem Cell Properties.","authors":"Hirotaka Konishi, Fitriana N Rahmawati, Naoki Okamoto, Keigo Akuta, Koichi Inukai, Weizhen Jia, Fumitaka Muramatsu, Nobuyuki Takakura","doi":"10.1080/10985549.2023.2297997","DOIUrl":"10.1080/10985549.2023.2297997","url":null,"abstract":"A resident vascular endothelial stem cell (VESC) population expressing CD157 has been identified recently in mice. Herein, we identified transcription factors (TFs) regulating CD157 expression in endothelial cells (ECs) that were associated with drug resistance, angiogenesis, and EC proliferation. In the first screening, we detected 20 candidate TFs through the CD157 promoter and gene expression analyses. We found that 10 of the 20 TFs induced CD157 expression in ECs. We previously reported that 70% of CD157 VESCs were side population (SP) ECs that abundantly expressed ATP-binding cassette (ABC) transporters. Here, we found that the 10 TFs increased the expression of several ABC transporters in ECs and increased the proportion of SP ECs. Of these 10 TFs, we found that six (Atf3, Bhlhe40, Egr1, Egr2, Elf3, and Klf4) were involved in the manifestation of the SP phenotype. Furthermore, the six TFs enhanced tube formation and proliferation in ECs. Single-cell RNA sequence data in liver ECs suggested that Atf3 and Klf4 contributed to the production of CD157+ VESCs in the postnatal period. We concluded that Klf4 might be important for the development and maintenance of liver VESCs. Our work suggests that a TF network is involved in the differentiation hierarchy of VESCs.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"17-26"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10829836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512920","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 Non-Canonical Hippo Pathway Represses the Expression of ΔNp63. 非规范的 Hippo 通路抑制 ΔNp63 的表达

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-01-29 DOI: 10.1080/10985549.2023.2292037

Ana Maria Low-Calle, Hana Ghoneima, Nicholas Ortega, Adriana M Cuibus, Chen Katz, Carol Prives, Ron Prywes

{"title":"A Non-Canonical Hippo Pathway Represses the Expression of ΔNp63.","authors":"Ana Maria Low-Calle, Hana Ghoneima, Nicholas Ortega, Adriana M Cuibus, Chen Katz, Carol Prives, Ron Prywes","doi":"10.1080/10985549.2023.2292037","DOIUrl":"10.1080/10985549.2023.2292037","url":null,"abstract":"The p63 transcription factor, a member of the p53 family, plays an oncogenic role in squamous cell carcinomas, while in breast cancers its expression is often repressed. In the canonical conserved Hippo pathway, known to play a complex role in regulating growth of cancer cells, protein kinases MST1/2 and LATS1/2 act sequentially to phosphorylate and inhibit the YAP/TAZ transcription factors. We found that in MCF10A mammary epithelial cells as well as in squamous and breast cancer cell lines, expression of ΔNp63 RNA and protein is strongly repressed by inhibition of the Hippo pathway protein kinases. While MST1/2 and LATS1 are required for p63 expression, the next step of the pathway, namely phosphorylation and degradation of the YAP/TAZ transcriptional activators is not required for p63 repression. This suggests that regulation of p63 expression occurs by a noncanonical version of the Hippo pathway. We identified similarly regulated genes, suggesting the broader importance of this pathway. Interestingly, lowering p63 expression lead to increased YAP protein levels, indicating crosstalk of the YAP/TAZ-independent and -dependent branches of the Hippo pathway. These results, which reveal the intersection of the Hippo and p63 pathways, may prove useful for the control of their activities in cancer cells.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"27-42"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10829837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546857","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 Ashkenazi-Centric G334R Variant of TP53 is Severely Impaired for Transactivation but Retains Tumor Suppressor Function in a Mouse Model. 在小鼠模型中，以阿什肯纳齐为中心的 TP53 G334R 变体的反式激活功能严重受损，但仍具有抑瘤功能。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-11-08 DOI: 10.1080/10985549.2024.2421885

David C Stieg, Kaitlyn Casey, Bhanu Chandra Karisetty, Julia I-Ju Leu, Fiona Larkin, Peter Vogel, Jozef Madzo, Maureen E Murphy

{"title":"The Ashkenazi-Centric G334R Variant of TP53 is Severely Impaired for Transactivation but Retains Tumor Suppressor Function in a Mouse Model.","authors":"David C Stieg, Kaitlyn Casey, Bhanu Chandra Karisetty, Julia I-Ju Leu, Fiona Larkin, Peter Vogel, Jozef Madzo, Maureen E Murphy","doi":"10.1080/10985549.2024.2421885","DOIUrl":"10.1080/10985549.2024.2421885","url":null,"abstract":"Mutations in the TP53 tumor suppressor gene are the most abundant genetic occurrences in cancer. Some of these mutations lead to loss of function of p53 protein, some are gain of function, and some variants are hypomorphic (partially functional). Currently, there is no clinical distinction between different p53 mutations and cancer therapy or prognosis. Mutations in the oligomerization domain of p53 appear to be quite distinct in function, compared to mutations in the DNA binding domain. Here we show that, like other p53 oligomerization domain mutants, the Ashkenazi-specific G334R mutant accumulates to very high levels in cells and is significantly impaired for the transactivation of canonical p53 target genes. Surprisingly, we find that this mutant retains the ability to bind to consensus p53 target sites. A mouse model reveals that mice containing the G334R variant show increased predisposition to cancer, but only a fraction of these mice develop late-onset cancer. We show that the G334R variant retains the ability to interact with the SP1 transcription factor and contributes to the transactivation of joint SP1-p53 target genes. The combined evidence indicates that G334R is a unique oligomerization domain mutant that retains some tumor suppressor function.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"607-621"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624063","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

Effects of Phenylacetylglutamine on the Susceptibility of Atrial Fibrillation in Overpressure-Induced HF Mice. 苯乙酰谷氨酰胺对超压诱导高频小鼠心房颤动易感性的影响

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-05-10 DOI: 10.1080/10985549.2024.2345363

Hui Fu, Dengke Li, Wei Shuai, Bin Kong, Xi Wang, Yanhong Tang, He Huang, Congxin Huang

{"title":"Effects of Phenylacetylglutamine on the Susceptibility of Atrial Fibrillation in Overpressure-Induced HF Mice.","authors":"Hui Fu, Dengke Li, Wei Shuai, Bin Kong, Xi Wang, Yanhong Tang, He Huang, Congxin Huang","doi":"10.1080/10985549.2024.2345363","DOIUrl":"10.1080/10985549.2024.2345363","url":null,"abstract":"Phenylacetylglutamine (PAGln), a gut metabolite is substantially elevated in heart failure (HF). The increase of PAGln in plasma is associated with atrial fibrillation (AF), and contributes to AF pathogenesis. However, the role of PAGln in AF with HF remains uncertain. Therefore, this study aimed to determine the effect of PAGln on AF after HF. Thoracic aortic coarctation (TAC) created overpressure-induced HF mice for 4 weeks. Histopathology, biochemical, echocardiographic for assessment of cardiac function, and electrophysiological examination of several electrophysiological indexes (ERP, SNRT, and the occurrence rate of AF) were performed at the end of the HF mice model. We found that plasma PAGln levels were significantly elevated in PAGln-treated HF mice and that PAGln aggravated maladaptive structural remodeling and electrical remodeling, which aggravated the vulnerability of AF, shortened the ERP duration, prolonged the SNRT, increased the occurrence rate of AF in HF mice. Mechanistically, PAGln exacerbated ROS accumulation and increased the levels of phosphorylated PLB and CAMK II. Overall, PAGln played a vital role in promoting the occurrence of AF in HF mice by activating the CAMK II signaling pathway.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"149-163"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898511","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

Regulation of Betaine Homocysteine Methyltransferase by Liver Receptor Homolog-1 in the Methionine Cycle. 肝脏同源受体-1 在蛋氨酸循环中对甜菜碱同型半胱氨酸甲基转移酶的调控

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-05-28 DOI: 10.1080/10985549.2024.2354821

Hee-Kyung Han, Sulagna Mukherjee, Soo-Young Park, Jae-Ho Lee, Eun-Ho Lee, Suji Kim, Yun Han Lee, Dae-Kyu Song, Sooyeun Lee, Jae-Hoon Bae, Seung-Soon Im

{"title":"Regulation of Betaine Homocysteine Methyltransferase by Liver Receptor Homolog-1 in the Methionine Cycle.","authors":"Hee-Kyung Han, Sulagna Mukherjee, Soo-Young Park, Jae-Ho Lee, Eun-Ho Lee, Suji Kim, Yun Han Lee, Dae-Kyu Song, Sooyeun Lee, Jae-Hoon Bae, Seung-Soon Im","doi":"10.1080/10985549.2024.2354821","DOIUrl":"10.1080/10985549.2024.2354821","url":null,"abstract":"Betaine-homocysteine S-methyltransferase (BHMT) is one of the most abundant proteins in the liver and regulates homocysteine metabolism. However, the molecular mechanisms underlying Bhmt transcription have not yet been elucidated. This study aimed to assess the molecular mechanisms underlying Bhmt transcription and the effect of BHMT deficiency on metabolic functions in the liver mediated by liver receptor homolog-1 (LRH-1). During fasting, both Bhmt and Lrh-1 expression increased in the liver of Lrh-1f/f mice; however, Bhmt expression was decreased in LRH-1 liver specific knockout mice. Promoter activity analysis confirmed that LRH-1 binds to a specific site in the Bhmt promoter region. LRH-1 deficiency was associated with elevated production of reactive oxygen species (ROS), lipid peroxidation, and mitochondrial stress in hepatocytes, contributing to hepatic triglyceride (TG) accumulation. In conclusion, this study suggests that the absence of an LRH-1-mediated decrease in Bhmt expression promotes TG accumulation by increasing ROS levels and inducing mitochondrial stress. Therefore, LRH-1 deficiency not only leads to excess ROS production and mitochondrial stress in hepatocytes, but also disrupts the methionine cycle. Understanding these regulatory pathways may pave the way for novel therapeutic interventions against metabolic disorders associated with hepatic lipid accumulation.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"245-258"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11204035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158000","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

MANCR lncRNA Modulates Cell-Cycle Progression and Metastasis by Cis-Regulation of Nuclear Rho-GEF. MANCR lncRNA通过核Rho-GEF的顺式调控调节细胞周期进展和转移。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-08-12 DOI: 10.1080/10985549.2024.2383773

Deepak K Singh, Zhengmin Cong, You Jin Song, Minxue Liu, Ritu Chaudhary, Dazhen Liu, Yu Wang, Rishabh Prasanth, Rajendra K C, Simon Lizarazo, Miriam Akhnoukh, Omid Gholamalamdari, Anurupa Moitra, Lisa M Jenkins, Rohit Bhargava, Erik R Nelson, Kevin Van Bortle, Supriya G Prasanth, Kannanganattu V Prasanth

{"title":"MANCR lncRNA Modulates Cell-Cycle Progression and Metastasis by Cis-Regulation of Nuclear Rho-GEF.","authors":"Deepak K Singh, Zhengmin Cong, You Jin Song, Minxue Liu, Ritu Chaudhary, Dazhen Liu, Yu Wang, Rishabh Prasanth, Rajendra K C, Simon Lizarazo, Miriam Akhnoukh, Omid Gholamalamdari, Anurupa Moitra, Lisa M Jenkins, Rohit Bhargava, Erik R Nelson, Kevin Van Bortle, Supriya G Prasanth, Kannanganattu V Prasanth","doi":"10.1080/10985549.2024.2383773","DOIUrl":"10.1080/10985549.2024.2383773","url":null,"abstract":"A significant number of the genetic alterations observed in cancer patients lie within nonprotein-coding segments of the genome, including regions coding for long noncoding RNAs (lncRNAs). LncRNAs display aberrant expression in breast cancer (BrCa), but the functional implications of this altered expression remain to be elucidated. By performing transcriptome screen in a triple negative BrCa (TNBC) isogenic 2D and 3D spheroid model, we observed aberrant expression of >1000 lncRNAs during BrCa progression. The chromatin-associated lncRNA MANCR shows elevated expression in metastatic TNBC. MANCR is upregulated in response to cellular stress and modulates DNA repair and cell proliferation. MANCR promotes metastasis as MANCR-depleted cells show reduced cell migration, invasion, and wound healing in vitro, and reduced metastatic lung colonization in xenograft experiments in vivo. Transcriptome analyses reveal that MANCR modulates expression and pre-mRNA splicing of genes, controlling DNA repair and checkpoint response. MANCR promotes the transcription of NET1A, a Rho-GEF that regulates DNA damage checkpoint and metastatic processes in cis, by differential promoter usage. Experiments suggest that MANCR regulates the expression of cancer-associated genes by modulating the association of various transcription factors and RNA-binding proteins. Our results identified the metastasis-promoting activities of MANCR in TNBC by cis-regulation of gene expression.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"372-390"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917112","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

β-TrCP-Mediated Proteolysis of Mis18β Prevents Mislocalization of CENP-A and Chromosomal Instability. β-TrCP介导的Mis18β蛋白水解可防止CENP-A的错定位和染色体不稳定性。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-08-13 DOI: 10.1080/10985549.2024.2382445

Subhash Chandra Sethi, Roshan Lal Shrestha, Vinutha Balachandra, Geetha Durairaj, Wei-Chun Au, Michael Nirula, Tatiana S Karpova, Peter Kaiser, Munira A Basrai

{"title":"β-TrCP-Mediated Proteolysis of Mis18β Prevents Mislocalization of CENP-A and Chromosomal Instability.","authors":"Subhash Chandra Sethi, Roshan Lal Shrestha, Vinutha Balachandra, Geetha Durairaj, Wei-Chun Au, Michael Nirula, Tatiana S Karpova, Peter Kaiser, Munira A Basrai","doi":"10.1080/10985549.2024.2382445","DOIUrl":"10.1080/10985549.2024.2382445","url":null,"abstract":"Restricting the localization of evolutionarily conserved histone H3 variant CENP-A to the centromere is essential to prevent chromosomal instability (CIN), an important hallmark of cancers. Overexpressed CENP-A mislocalizes to non-centromeric regions and contributes to CIN in yeast, flies, and human cells. Centromeric localization of CENP-A is facilitated by the interaction of Mis18β with CENP-A specific chaperone HJURP. Cellular levels of Mis18β are regulated by β-transducin repeat containing protein (β-TrCP), an F-box protein of SCF (Skp1, Cullin, F-box) E3-ubiquitin ligase complex. Here, we show that defects in β-TrCP-mediated proteolysis of Mis18β contributes to the mislocalization of endogenous CENP-A and CIN in a triple-negative breast cancer (TNBC) cell line, MDA-MB-231. CENP-A mislocalization in β-TrCP depleted cells is dependent on high levels of Mis18β as depletion of Mis18β suppresses mislocalization of CENP-A in these cells. Consistent with these results, endogenous CENP-A is mislocalized in cells overexpressing Mis18β alone. In summary, our results show that β-TrCP-mediated degradation of Mis18β prevents mislocalization of CENP-A and CIN. We propose that deregulated expression of Mis18β may be one of the key mechanisms that contributes to chromosome segregation defects in cancers.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"429-442"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971473","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 Factor 23 is an Essential Determinant of Murine Term Parturition. 转录因子 23 是小鼠临产的重要决定因素

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-07-16 DOI: 10.1080/10985549.2024.2376146

Fatma M Minisy, Hossam H Shawki, Tsubasa Fujita, Ahmed M Moustafa, Rumeysa Sener, Youske Nishio, Issei S Shimada, Shinji Saitoh, Mayumi Sugiura-Ogasawara, Hisashi Oishi

{"title":"Transcription Factor 23 is an Essential Determinant of Murine Term Parturition.","authors":"Fatma M Minisy, Hossam H Shawki, Tsubasa Fujita, Ahmed M Moustafa, Rumeysa Sener, Youske Nishio, Issei S Shimada, Shinji Saitoh, Mayumi Sugiura-Ogasawara, Hisashi Oishi","doi":"10.1080/10985549.2024.2376146","DOIUrl":"10.1080/10985549.2024.2376146","url":null,"abstract":"Pregnancy involving intricate tissue transformations governed by the progesterone hormone (P4). P4 signaling via P4 receptors (PRs) is vital for endometrial receptivity, decidualization, myometrial quiescence, and labor initiation. This study explored the role of TCF23 as a downstream target of PR during pregnancy. TCF23 was found to be expressed in female reproductive organs, predominantly in uterine stromal and smooth muscle cells. Tcf23 expression was high during midgestation and was specifically regulated by P4, but not estrogen. The Tcf23 knockout (KO) mouse was generated and analyzed. Female KO mice aged 4-6 months exhibited subfertility, reduced litter size, and defective parturition. Uterine histology revealed disrupted myometrial structure, altered collagen organization, and disarrayed smooth muscle sheets at the conceptus sites of KO mice. RNA-Seq analysis of KO myometrium revealed dysregulation of genes associated with cell adhesion and extracellular matrix organization. TCF23 potentially modulates TCF12 activity to mediate cell-cell adhesion and matrix modulation in smooth muscle cells. Overall, TCF23 deficiency leads to impaired myometrial remodeling, causing parturition delay and fetal demise. This study sheds light on the critical role of TCF23 as a dowstream mediator of PR in uterine remodeling, reflecting the importance of cell-cell communication and matrix dynamics in myometrial activation and parturition.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"316-333"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627155","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

NatB Protects Procaspase-8 from UBR4-Mediated Degradation and Is Required for Full Induction of the Extrinsic Apoptosis Pathway. NatB 保护 Procaspase-8 免受 UBR4 介导的降解，是全面诱导凋亡外途径的必要条件

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2024-01-01 Epub Date: 2024-08-04 DOI: 10.1080/10985549.2024.2382453

Joana P Guedes, Jean Baptiste Boyer, Jasmine Elurbide, Beatriz Carte, Virginie Redeker, Laila Sago, Thierry Meinnel, Manuela Côrte-Real, Carmela Giglione, Rafael Aldabe

{"title":"NatB Protects Procaspase-8 from UBR4-Mediated Degradation and Is Required for Full Induction of the Extrinsic Apoptosis Pathway.","authors":"Joana P Guedes, Jean Baptiste Boyer, Jasmine Elurbide, Beatriz Carte, Virginie Redeker, Laila Sago, Thierry Meinnel, Manuela Côrte-Real, Carmela Giglione, Rafael Aldabe","doi":"10.1080/10985549.2024.2382453","DOIUrl":"10.1080/10985549.2024.2382453","url":null,"abstract":"N-terminal acetyltransferase B (NatB) is a major contributor to the N-terminal acetylome and is implicated in several key cellular processes including apoptosis and proteostasis. However, the molecular mechanisms linking NatB-mediated N-terminal acetylation to apoptosis and its relationship with protein homeostasis remain elusive. In this study, we generated mouse embryonic fibroblasts (MEFs) with an inactivated catalytic subunit of NatB (Naa20-/-) to investigate the impact of NatB deficiency on apoptosis regulation. Through quantitative N-terminomics, label-free quantification, and targeted proteomics, we demonstrated that NatB does not influence the proteostasis of all its substrates. Instead, our focus on putative NatB-dependent apoptotic factors revealed that NatB serves as a protective shield against UBR4 and UBR1 Arg/N-recognin-mediated degradation. Notably, Naa20-/- MEFs exhibited reduced responsiveness to an extrinsic pro-apoptotic stimulus, a phenotype that was partially reversible upon UBR4 Arg/N-recognin silencing and consequent inhibition of procaspase-8 degradation. Collectively, our results shed light on how the interplay between NatB-mediated acetylation and the Arg/N-degron pathway appears to impact apoptosis regulation, providing new perspectives in the field including in therapeutic interventions.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"358-371"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889774","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