{"title":"Retraction: Lead induces the upregulation of protein arginine methyltransferase 5 possibly by its promoter demethylation.","authors":"","doi":"10.1042/bcj20180167_ret","DOIUrl":"https://doi.org/10.1042/bcj20180167_ret","url":null,"abstract":"","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"39 1","pages":"365"},"PeriodicalIF":4.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827099","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}
{"title":"Retraction: Lead induces the upregulation of protein arginine methyltransferase 5 possibly by its promoter demethylation.","authors":"","doi":"10.1042/bcj20180009_ret","DOIUrl":"https://doi.org/10.1042/bcj20180009_ret","url":null,"abstract":"","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"23 1","pages":"367"},"PeriodicalIF":4.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827118","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}
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":"<p><p>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.</p>","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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction: Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms.","authors":"","doi":"10.1042/BCJ20200937_COR","DOIUrl":"https://doi.org/10.1042/BCJ20200937_COR","url":null,"abstract":"","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"482 7","pages":"357-358"},"PeriodicalIF":4.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975912","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}
{"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":"https://doi.org/10.1042/BCJ20240683","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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":"https://doi.org/10.1042/BCJ20253036","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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":"https://doi.org/10.1042/BCJ20240726","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"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":"<p><p>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.</p>","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}