Biochemical Journal最新文献_第6页

Ring finger protein 138 inhibits transcription factor C/EBPα protein turnover leading to differentiation arrest in acute myeloid leukemia. RNF138 可抑制转录因子 C/EBPα 蛋白的周转，导致急性髓细胞性白血病的分化停滞。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2024-05-22 DOI: 10.1042/BCJ20240027

Anil Kumar Singh, Vishal Upadhyay, Arppita Sethi, Sangita Chowdhury, Shivkant Mishra, Shailendra Prasad Verma, Madan Lal Brahma Bhatt, Arun Kumar Trivedi

{"title":"Ring finger protein 138 inhibits transcription factor C/EBPα protein turnover leading to differentiation arrest in acute myeloid leukemia.","authors":"Anil Kumar Singh, Vishal Upadhyay, Arppita Sethi, Sangita Chowdhury, Shivkant Mishra, Shailendra Prasad Verma, Madan Lal Brahma Bhatt, Arun Kumar Trivedi","doi":"10.1042/BCJ20240027","DOIUrl":"10.1042/BCJ20240027","url":null,"abstract":"E3 ubiquitin ligase, ring finger protein 138 (RNF138) is involved in several biological processes; however, its role in myeloid differentiation or tumorigenesis remains unclear. RNAseq data from TNMplot showed that RNF138 mRNA levels are highly elevated in acute myeloid leukemia (AML) bone marrow samples as compared with bone marrow of normal volunteers. Here, we show that RNF138 serves as an E3 ligase for the tumor suppressor CCAAT/enhancer binding protein (C/EBPα) and promotes its degradation leading to myeloid differentiation arrest in AML. Wild-type RNF138 physically interacts with C/EBPα and promotes its ubiquitin-dependent proteasome degradation while a mutant RNF-138 deficient in ligase activity though interacts with C/EBPα, fails to down-regulate it. We show that RNF138 depletion enhances endogenous C/EBPα levels in peripheral blood mononuclear cells (PBMCs) isolated from healthy volunteers. Our data further shows that RNF138-mediated degradation of C/EBPα negatively affects its transactivation potential on its target genes. Furthermore, RNF138 overexpression inhibits all-trans-retinoic acid-induced differentiation of HL-60 cells whereas RNF138 RNAi enhances. In line with RNF138 inhibiting C/EBPα protein turnover, we also observed that RNF138 overexpression inhibited β-estradiol (E2)-induced C/EBPα driven granulocytic differentiation in C/EBPα inducible K562-p42C/EBPα-estrogen receptor cells. Furthermore, we also recapitulated these findings in PBMCs isolated from AML patients where depletion of RNF138 increased the expression of myeloid differentiation marker CD11b. These results suggest that RNF138 inhibits myeloid differentiation by targeting C/EBPα for proteasomal degradation and may provide a plausible mechanism for loss of C/EBPα expression often observed in myeloid leukemia. Also, targeting RNF138 may resolve differentiation arrest by restoring C/EBPα expression in AML.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"653-666"},"PeriodicalIF":4.4,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: The uncharacterized Pseudomonas aeruginosa PA4189 is a novel and efficient aminoacetaldehyde dehydrogenase. 更正：未定性的铜绿假单胞菌 PA4189 是一种新型高效的氨基乙醛脱氢酶。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2024-05-22 DOI: 10.1042/BCJ20220567_COR

Arline Fernández-Silva Ana L Juárez-Vázquez Lilian González-Segura Javier Andrés Juárez-Díaz Rosario A Muñoz-Clares

引用次数: 0

Expression of neuronal NO synthase α- and β-isoforms in skeletal muscle of mice 小鼠骨骼肌中神经元 NO 合酶 α 和 β 异构体的表达

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2024-05-08 DOI: 10.1042/bcj20230458

Baum, Oliver

{"title":"Expression of neuronal NO synthase α- and β-isoforms in skeletal muscle of mice","authors":"Baum, Oliver","doi":"10.1042/bcj20230458","DOIUrl":"https://doi.org/10.1042/bcj20230458","url":null,"abstract":"Knowledge of the primary structure of neuronal NO synthase (nNOS) in skeletal muscle is still conflicting and needs further clarification. To elucidate the expression patterns of nNOS isoforms at both mRNA and protein level, systematic reverse transcription (RT)-PCR and epitope mapping by qualitative immunoblot analysis on skeletal muscle of C57/BL6 mice were performed. The ability of the nNOS isoforms to form aggregates was characterized by native low-temperature polyacrylamide electrophoresis (LT-PAGE). The molecular analysis was focused on the rectus femoris (RF) muscle, a skeletal muscle with a nearly balanced ratio of nNOS α- and β-isoforms. RT-PCR amplificates from RF muscles showed exclusive exon-1d mRNA expression, either with or without exon-μ. Epitope mapping demonstrated the simultaneous expression of the nNOS splice variants α/μ, α/non-μ, β/μ and β/non-μ. Furthermore, immunoblotting suggests that the transition between nNOS α- and β-isoforms lies within exon-3. In LT-PAGE, three protein nNOS associated aggregates were detected in homogenates of RF muscle and tibialis anterior muscle: a 320 kDa band containing nNOS α-isoforms, while 250 and 300 kDa bands consist of nNOS β-isoforms that form homodimers or heterodimers with non-nNOS proteins.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"7 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140642296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biochemical and structural impact of two novel missense mutations in cystathionine β-synthase gene associated with homocystinuria. 与高胱氨酸尿症相关的胱硫醚-β-合成酶基因中两种新型错义突变的生化和结构影响。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2024-04-24 DOI: 10.1042/BCJ20240012

Duaa W Al-Sadeq, Carolina Conter, Angelos Thanassoulas, Nader Al-Dewik, Bared Safieh-Garabedian, Luis Alfonso Martínez-Cruz, Gheyath K Nasrallah, Alessandra Astegno, Michail Nomikos

{"title":"Biochemical and structural impact of two novel missense mutations in cystathionine β-synthase gene associated with homocystinuria.","authors":"Duaa W Al-Sadeq, Carolina Conter, Angelos Thanassoulas, Nader Al-Dewik, Bared Safieh-Garabedian, Luis Alfonso Martínez-Cruz, Gheyath K Nasrallah, Alessandra Astegno, Michail Nomikos","doi":"10.1042/BCJ20240012","DOIUrl":"10.1042/BCJ20240012","url":null,"abstract":"Homocystinuria is a rare disease caused by mutations in the CBS gene that results in a deficiency of cystathionine β-synthase (CBS). CBS is an essential pyridoxal 5'-phosphate (PLP)-dependent enzyme in the transsulfuration pathway, responsible for combining serine with homocysteine to produce cystathionine, whose activity is enhanced by the allosteric regulator S-adenosylmethionine (SAM). CBS also plays a role in generating hydrogen sulfide (H2S), a gaseous signaling molecule with diverse regulatory functions within the vascular, nervous, and immune systems. In this study, we present the clinical and biochemical characterization of two novel CBS missense mutations that do not respond to pyridoxine treatment, namely c.689T > A (L230Q) and 215A > T (K72I), identified in a Chinese patient. We observed that the disease-associated K72I genetic variant had no apparent effects on the spectroscopic and catalytic properties of the full-length enzyme. In contrast, the L230Q variant expressed in Escherichia coli did not fully retain heme and when compared with the wild-type enzyme, it exhibited more significant impairments in both the canonical cystathionine-synthesis and the alternative H2S-producing reactions. This reduced activity is consistent with both in vitro and in silico evidence, which indicates that the L230Q mutation significantly decreases the overall protein's stability, which in turn, may represent the underlying cause of its pathogenicity.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"569-585"},"PeriodicalIF":4.1,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AMP-activated protein kinase can be allosterically activated by ADP but AMP remains the key activating ligand AMP 激活的蛋白激酶可被 ADP 异源激活，但 AMP 仍是关键的激活配体

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2024-04-24 DOI: 10.1042/bcj20240082

Hawley, Simon A., Russell, Fiona M., Hardie, D. Grahame

{"title":"AMP-activated protein kinase can be allosterically activated by ADP but AMP remains the key activating ligand","authors":"Hawley, Simon A., Russell, Fiona M., Hardie, D. Grahame","doi":"10.1042/bcj20240082","DOIUrl":"https://doi.org/10.1042/bcj20240082","url":null,"abstract":"The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. When activated by increases in ADP:ATP and/or AMP:ATP ratios (signalling energy deficit), AMPK acts to restore energy balance. Binding of AMP to one or more of three CBS repeats (CBS1, CBS3, CBS4) on the AMPK-γ subunit activates the kinase complex by three complementary mechanisms: (i) promoting α-subunit Thr172 phosphorylation by the upstream kinase LKB1; (ii) protecting against Thr172 dephosphorylation; (iii) allosteric activation. Surprisingly, binding of ADP has been reported to mimic the first two effects, but not the third. We now show that at physiologically relevant concentrations of Mg.ATP2− (above those used in the standard assay) ADP binding does cause allosteric activation. However, ADP causes only a modest activation because (unlike AMP), at concentrations just above those where activation becomes evident, ADP starts to cause competitive inhibition at the catalytic site. Our results cast doubt on the physiological relevance of the effects of ADP and suggest that AMP is the primary activator in vivo. We have also made mutations to hydrophobic residues involved in binding adenine nucleotides at each of the three γ subunit CBS repeats of the human α2β2γ1 complex and examined their effects on regulation by AMP and ADP. Mutation of the CBS3 site has the largest effects on all three mechanisms of AMP activation, especially at lower ATP concentrations, while mutation of CBS4 reduces the sensitivity to AMP. All three sites appear to be required for allosteric activation by ADP.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"102 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2α phosphorylation. 有证据表明，Xrn1 与 Gcn1 复合物，是全水平 eIF2α 磷酸化所必需的。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2024-04-10 DOI: 10.1042/BCJ20220531

Renuka Shanmugam, Reuben Anderson, Anja H Schiemann, Evelyn Sattlegger

{"title":"Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2α phosphorylation.","authors":"Renuka Shanmugam, Reuben Anderson, Anja H Schiemann, Evelyn Sattlegger","doi":"10.1042/BCJ20220531","DOIUrl":"10.1042/BCJ20220531","url":null,"abstract":"The protein kinase Gcn2 and its effector protein Gcn1 are part of the general amino acid control signalling (GAAC) pathway best known in yeast for its function in maintaining amino acid homeostasis. Under amino acid limitation, Gcn2 becomes activated, subsequently increasing the levels of phosphorylated eIF2α (eIF2α-P). This leads to the increased translation of transcriptional regulators, such as Gcn4 in yeast and ATF4 in mammals, and subsequent re-programming of the cell's gene transcription profile, thereby allowing cells to cope with starvation. Xrn1 is involved in RNA decay, quality control and processing. We found that Xrn1 co-precipitates Gcn1 and Gcn2, suggesting that these three proteins are in the same complex. Growth under starvation conditions was dependent on Xrn1 but not on Xrn1-ribosome association, and this correlated with reduced eIF2α-P levels. Constitutively active Gcn2 leads to a growth defect due to eIF2α-hyperphosphorylation, and we found that this phenotype was independent of Xrn1, suggesting that xrn1 deletion does not enhance eIF2α de-phosphorylation. Our study provides evidence that Xrn1 is required for efficient Gcn2 activation, directly or indirectly. Thus, we have uncovered a potential new link between RNA metabolism and the GAAC.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"481-498"},"PeriodicalIF":4.1,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: Proteasome and thiol involvement in quality control of glycosylphosphatidylinositol anchor addition 更正：蛋白酶体和硫醇参与糖基磷脂酰肌醇锚添加的质量控制

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2024-04-10 DOI: 10.1042/bj3320111_cor

Wilbourn, Barry, Nesbeth, Darren N., Wainwright, Linda J., Field, Mark C.

引用次数: 0

Long-range electron proton coupling in respiratory complex I — insights from molecular simulations of the quinone chamber and antiporter-like subunits 呼吸复合体 I 中的长程电子质子耦合--从醌室和类逆流器亚基的分子模拟中获得的启示

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2024-04-10 DOI: 10.1042/bcj20240009

Djurabekova, Amina, Lasham, Jonathan, Zdorevskyi, Oleksii, Zickermann, Volker, Sharma, Vivek

引用次数: 0

Expression of Concern: Protease-activated receptor-2 promotes kidney tubular epithelial inflammation by inhibiting autophagy via the PI3K/Akt/mTOR signalling pathway 关注表达：蛋白酶激活受体-2通过PI3K/Akt/mTOR信号通路抑制自噬，从而促进肾小管上皮细胞炎症

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2024-04-10 DOI: 10.1042/bcj20170272_eoc

Du, Chunyang, Zhang, Tao, Xiao, Xia, Shi, Yonghong, Duan, Huijun, Ren, Yunzhuo

引用次数: 0

Activin E is a transforming growth factor β ligand that signals specifically through activin receptor-like kinase 7. 激活素 E 是一种 TGFβ 配体，可通过激活素受体样激酶 7 发出特异性信号。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2024-04-10 DOI: 10.1042/BCJ20230404

Kylie A Vestal, Chandramohan Kattamuri, Muhasin Koyiloth, Luisina Ongaro, James A Howard, Aimee M Deaton, Simina Ticau, Aditi Dubey, Daniel J Bernard, Thomas B Thompson

{"title":"Activin E is a transforming growth factor β ligand that signals specifically through activin receptor-like kinase 7.","authors":"Kylie A Vestal, Chandramohan Kattamuri, Muhasin Koyiloth, Luisina Ongaro, James A Howard, Aimee M Deaton, Simina Ticau, Aditi Dubey, Daniel J Bernard, Thomas B Thompson","doi":"10.1042/BCJ20230404","DOIUrl":"10.1042/BCJ20230404","url":null,"abstract":"Activins are one of the three distinct subclasses within the greater Transforming growth factor β (TGFβ) superfamily. First discovered for their critical roles in reproductive biology, activins have since been shown to alter cellular differentiation and proliferation. At present, members of the activin subclass include activin A (ActA), ActB, ActC, ActE, and the more distant members myostatin and GDF11. While the biological roles and signaling mechanisms of most activins class members have been well-studied, the signaling potential of ActE has remained largely unknown. Here, we characterized the signaling capacity of homodimeric ActE. Molecular modeling of the ligand:receptor complexes showed that ActC and ActE shared high similarity in both the type I and type II receptor binding epitopes. ActE signaled specifically through ALK7, utilized the canonical activin type II receptors, ActRIIA and ActRIIB, and was resistant to the extracellular antagonists follistatin and WFIKKN. In mature murine adipocytes, ActE invoked a SMAD2/3 response via ALK7, like ActC. Collectively, our results establish ActE as a specific signaling ligand which activates the type I receptor, ALK7.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"547-564"},"PeriodicalIF":4.1,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140292629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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