Biochemical Journal最新文献_第5页

Correction: Ionizing radiation induces ataxia telangiectasia mutated kinase (ATM)-mediated phosphorylation of LKB1/STK11 at Thr-366. 更正：电离辐射诱导共济失调毛细血管扩张突变激酶（ATM）介导的LKB1/STK11在Thr-366位点的磷酸化。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-04-10 DOI: 10.1042/BJ20021284_COR

引用次数: 0

The PRL2 phosphatase up-regulates miR-21 through activation of the JAK2/STAT3 pathway to down-regulate the PTEN tumor suppressor. PRL2磷酸酶通过激活JAK2/STAT3通路上调miR-21，下调PTEN肿瘤抑制因子。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-04-10 DOI: 10.1042/BCJ20240626

Qinglin Li, Yunpeng Bai, Sarah M Cavender, Yiming Miao, Frederick Nguele Meke, Emily L Lasse-Opsahl, Peipei Zhu, Gina M Doody, W Andy Tao, Zhong-Yin Zhang

{"title":"The PRL2 phosphatase up-regulates miR-21 through activation of the JAK2/STAT3 pathway to down-regulate the PTEN tumor suppressor.","authors":"Qinglin Li, Yunpeng Bai, Sarah M Cavender, Yiming Miao, Frederick Nguele Meke, Emily L Lasse-Opsahl, Peipei Zhu, Gina M Doody, W Andy Tao, Zhong-Yin Zhang","doi":"10.1042/BCJ20240626","DOIUrl":"10.1042/BCJ20240626","url":null,"abstract":"The phosphatases of regenerating liver (PRLs) are members of the protein tyrosine phosphatase (PTP) superfamily that play pro-oncogenic roles in cell proliferation, migration, and survival. We previously demonstrated that PRLs can post-translationally down-regulate PTEN, a tumor suppressor frequently inactivated in human cancers, by dephosphorylating PTEN at Tyr336, which promotes the NEDD4-mediated PTEN ubiquitination and proteasomal degradation. Here, we report that PRLs can also reduce PTEN expression by up-regulating microRNA-21 (miR-21), which is one of the most frequently overexpressed miRNAs in solid tumors. We observe a broad correlation between PRL and miR-21 levels in multiple human cancers. Mechanistically, PRL2, the most abundant and ubiquitously expressed PRL family member, promotes the JAK2/STAT3 pathway-mediated miR-21 expression by directly dephosphorylating JAK2 at Tyr570. Finally, we confirm that the PRL2-mediated miR-21 expression contributes to its oncogenic potential in breast cancer cells. Our study defines a new functional role of PRL2 in PTEN regulation through a miR-21-dependent post-transcriptional mechanism, in addition to our previously reported NEDD4-dependent post-translational PTEN regulation. Together, these studies further establish the PRLs as negative regulators of PTEN.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"341-356"},"PeriodicalIF":4.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812135","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: Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms. 纠正：破译LRRK密码：LRRK1和LRRK2磷酸化不同的Rab蛋白，并受到多种机制的调节。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-04-10 DOI: 10.1042/BCJ20200937_COR

引用次数: 0

Paraquat resistance mutations have differential effects on plant fitness in two rice cultivars. 抗百草枯突变对两个水稻品种的植株适合度有不同的影响。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-04-08 DOI: 10.1042/BCJ20240683

Jared B Fudge, Teresa B Fitzpatrick

{"title":"Paraquat resistance mutations have differential effects on plant fitness in two rice cultivars.","authors":"Jared B Fudge, Teresa B Fitzpatrick","doi":"10.1042/BCJ20240683","DOIUrl":"10.1042/BCJ20240683","url":null,"abstract":"Paraquat is a fast-acting non-selective herbicide widely used globally to eradicate weeds. The emergence of weed resistance has fueled the drive to understand molecular mechanistic aspects and develop crops resistant to the herbicide. The transport of paraquat is mediated by members of the L-amino acid transporter family and are prime targets for the development of resistance. However, these transporters also facilitate the transport of natural essential molecules such as polyamines and thiamine (vitamin B1), at least in Arabidopsis, but have not undergone rigorous investigation in crops. Here we report on disruption of the polyamine transporter PUT3 in two japonica rice cultivars. Both rice put3 mutant alleles are resistant to paraquat and display low percentage germination concomitant with altered polyamine profiles whereas thiamine is unchanged. Notwithstanding, seedlings that germinate behave like wild type in the Tainung 67 cultivar, whereas further growth and development is strongly impaired by disruption of PUT3 in the Hwayoung cultivar. The growth phenotype could be complemented by ectopic expression of PUT3, which also restores the polyamine profile thus linking the defects to disruption of the gene. Our study provides biological insight into the divergent characteristics of rice cultivar tissues as a function of their polyamine profile and a warning to exercise caution upon disruption of transporters to facilitate paraquat resistance in crops as this may also lead to severe fitness penalties.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810087","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

Dynamic Interchange of Local Residue-Residue Interactions in the Largely Extended Single Alpha-Helix in Drebrin. 大扩展单α -螺旋中局部残基-残基相互作用的动态交换。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-04-01 DOI: 10.1042/BCJ20253036

Soma Varga, Bálint Ferenc Péterfia, Dániel Dudola, Viktor Farkas, Cy M Jeffries, Perttu Permi, Zoltán Gáspári

{"title":"Dynamic Interchange of Local Residue-Residue Interactions in the Largely Extended Single Alpha-Helix in Drebrin.","authors":"Soma Varga, Bálint Ferenc Péterfia, Dániel Dudola, Viktor Farkas, Cy M Jeffries, Perttu Permi, Zoltán Gáspári","doi":"10.1042/BCJ20253036","DOIUrl":"10.1042/BCJ20253036","url":null,"abstract":"Single alpha-helices (SAHs) are protein regions with unique mechanical properties, forming long stable monomeric helical structures in solution. To date, only a few naturally occurring SAH regions have been extensively characterized, primarily from myosins, leaving the structural and dynamic variability of SAH regions largely unexplored. Drebrin (developmentally regulated brain protein) contains a predicted SAH segment with unique sequence characteristics, including aromatic residues within the SAH region and a preference for arginine over lysine in its C-terminal half. Using and NMR spectroscopy, combined with SAXS measurements, we demonstrate that the Drebrin-SAH is helical and monomeric in solution. NMR resonance assignment required specific 4D techniques to resolve severe signal overlap resulting from the low complexity and largely helical conformation of the sequence. To further characterize its structure, we generated a structural ensemble consistent with Cα, Cβ chemical shifts and SAXS data, revealing a primarily extended structure with non-uniform helicity. Our results suggest that dynamic rearrangement of salt bridges and potential transient cation-π interactions contribute to the formation and stabilization of both helical and non-helical local conformational states.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794600","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

Aurora A binds to the transactivation domain of c-Myc and recognizes the phosphorylated N-terminal degron motif. Aurora A结合到c-Myc的转激活域并识别磷酸化的n端脱基序。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-03-28 DOI: 10.1042/BCJ20240726

Nidhi Joshi, Katie M Dunleavy, Kaitlin M Beel, Tiffany A Engel, Andrew R Thompson, Felix L John, David D Thomas, Nicholas M Levinson

{"title":"Aurora A binds to the transactivation domain of c-Myc and recognizes the phosphorylated N-terminal degron motif.","authors":"Nidhi Joshi, Katie M Dunleavy, Kaitlin M Beel, Tiffany A Engel, Andrew R Thompson, Felix L John, David D Thomas, Nicholas M Levinson","doi":"10.1042/BCJ20240726","DOIUrl":"10.1042/BCJ20240726","url":null,"abstract":"The oncoprotein c-Myc is overexpressed or mutated in a large fraction of human cancers. The stability of c-Myc is controlled by phosphorylation of T58 and S62 within a conserved degron motif in the N-terminal transactivation domain, which triggers recruitment of the SCF ubiquitin ligase. The kinase Aurora A (AurA) has been shown to bind to both c-Myc and its paralog N-Myc and to promote their stability by interfering with ubiquitination and degradation. Here we show, using NMR and FRET experiments, that AurA binds to c-Myc through several discrete interactions spanning 145 residues within its transactivation domain. AurA binding to c-Myc is enhanced by phosphorylation of the T58/S62 degron, demonstrating that the kinase recognizes the pool of c-Myc that has been marked for degradation by the ubiquitin proteasome pathway. Although AurA binds to segments of c-Myc flanking the degron, it does not appear to form extensive interactions with the phosphorylated degron itself, potentially leaving it accessible on the AurA surface. These observations establish a foundation for understanding the role of AurA in regulating c-Myc ubiquitination and degradation.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771247","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

Sequence rules for a long SPOP-binding degron required for protein ubiquitylation. 蛋白质泛素化所需的长spop结合降解的序列规则。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-03-27 DOI: 10.1042/BCJ20253041

Linda Makhlouf, Mukul Mishra, Hannah Makhlouf, Iain Manfield, Luca Busino, Elton Zeqiraj

{"title":"Sequence rules for a long SPOP-binding degron required for protein ubiquitylation.","authors":"Linda Makhlouf, Mukul Mishra, Hannah Makhlouf, Iain Manfield, Luca Busino, Elton Zeqiraj","doi":"10.1042/BCJ20253041","DOIUrl":"https://doi.org/10.1042/BCJ20253041","url":null,"abstract":"The adaptor protein, Speckle-type BTB/POZ protein (SPOP), recruits substrates to the cullin-3-subclass of E3 ligase for selective protein ubiquitylation. The Myddosome protein, Myeloid differentiation primary response 88 (MyD88), is ubiquitylated by the SPOP-based E3 ligase to negatively regulate immune signaling, however, the sequence rules for SPOP-mediated substrate engagement and degradation are not fully understood. Here, we show that MyD88 interacts with SPOP through a long degron that contains the established SPOP-binding consensus and an N-terminal site that we name the Q-motif. Based on sequence similarity to MyD88, we show that additional substrates, including Steroid receptor coactivator-3 (SRC-3), SET domain-containing protein 2 (SETD2) and Caprin1, engage SPOP in this manner. We show that the Q-motif is a critical determinant of these interactions in mammalian cells and determine X-ray crystal structures that show the molecular basis of SPOP associations with these proteins. These studies reveal a new consensus sequence for substrate-binding to SPOP that is necessary for substrate ubiquitylation, thus expanding the sequence rules required for SPOP-mediated E3 ligase substrate recognition.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771251","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

Trypanosomatid histones: the building blocks of the epigenetic code of highly divergent eukaryotes. 锥虫组蛋白：高度分化的真核生物表观遗传密码的组成部分。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-03-14 DOI: 10.1042/BCJ20240543

Josefina Ocampo, Santiago Carena, María Del Rosario López, Valentina Sol Vela, Romina Trinidad Zambrano Siri, Sofia Antonella Balestra, Guillermo Daniel Alonso

{"title":"Trypanosomatid histones: the building blocks of the epigenetic code of highly divergent eukaryotes.","authors":"Josefina Ocampo, Santiago Carena, María Del Rosario López, Valentina Sol Vela, Romina Trinidad Zambrano Siri, Sofia Antonella Balestra, Guillermo Daniel Alonso","doi":"10.1042/BCJ20240543","DOIUrl":"10.1042/BCJ20240543","url":null,"abstract":"Histones play a fundamental role in eukaryotic organisms not only as scaffolding proteins in DNA packaging but also in regulating gene expression. They constitute the protein reel around which DNA wraps forming nucleosomes. This initial packing gives rise to the chromatin fiber which is next folded into three-dimensional arrangements. Additionally, histones have expanded their functions through the emergence of histone variants which have specialized purposes and can deeply affect chromatin organization and dynamics. Moreover, both canonical histones and histone variants comprise the building blocks of the histone code by being targets of different post-translational modifications (PTMs) that occur in a highly regulated manner both in place and time. Most of the above-mentioned about chromatin organization is conserved among eukaryotes. However, trypanosomatid histones have many peculiarities that entail a special description. In this review, we compile the current knowledge of canonical core histones, histone variants, and their PTMs in trypanosomatids. We highlight the similarities and differences between histone variants and their canonical counterparts in trypanosomatids, and we compare them with those from model organisms. Finally, we discuss the crosstalk between different histone marks and their genomic distribution underlying the uniqueness of trypanosomatids.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"482 6","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647061","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

Insights into the cellular function and mechanism of action of quinone reductase 2 (NQO2). 醌还原酶2 （NQO2）的细胞功能及作用机制研究。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-03-11 DOI: 10.1042/BCJ20240103

Faiza Islam, Brian Shilton

{"title":"Insights into the cellular function and mechanism of action of quinone reductase 2 (NQO2).","authors":"Faiza Islam, Brian Shilton","doi":"10.1042/BCJ20240103","DOIUrl":"10.1042/BCJ20240103","url":null,"abstract":"Quinone reductase 2 (NQO2) is a FAD-linked enzyme that cannot use the common reducing cofactors, NADH and NADPH, for efficient catalysis. This is unusual for an oxidoreductase, particularly since it is a member of a large family of enzymes that all use NAD(P)H efficiently to catalyse the two-electron reduction in quinones and other electrophiles. The inability of NQO2 to use NAD(P)H efficiently raises questions about its cellular function: it remains unclear whether the main cellular role of NQO2 is the catalytic reduction in quinones or whether it is a pseudo-enzyme with other roles such as cell signalling. Intriguingly, NQO2 has been identified as an off-target interactor with over 30 kinase inhibitors and other drugs and natural products. The interaction between NQO2 and kinase-targeted drugs is particularly intriguing because it suggests that NQO2 may be contributing to the cellular effects of these drugs. In this review, we will discuss the enzymatic properties of NQO2, its structure and complexes with various drugs and small molecules, potential cellular roles, and some of the enigmatic findings that make this molecule so interesting and worthy of further investigation.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"482 6","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603880","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

Aldose reductase, fructose and fat production in the liver. 醛糖还原酶，肝脏中果糖和脂肪的产生。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-03-05 DOI: 10.1042/BCJ20240748

Peter Delannoy, Dean R Tolan, Miguel A Lanaspa, Iñigo San Millán, So Young Bae, Richard J Johnson

引用次数: 0