Loss of the methylarginine reader function of SND1 confers resistance to hepatocellular carcinoma
Biochem J. 2023 Oct 31:BCJ20230384. doi: 10.1042/BCJ20230384. Online ahead of print.ABSTRACTStaphylococcal nuclease Tudor domain containing 1 (SND1) protein is an oncogene that "reads" methylarginine marks through its Tudor domain. Specifically, it recognizes methylation marks deposited by protein arginine methyltransferase 5 (PRMT5), which is also known to promote tumorigenesis. Although SND1 can drive hepatocellular carcinoma (HCC), it is unclear whether the SND1 Tudor domain is needed to promote HCC. We sought to identify the biological role of the SND1 Tudor domain in normal and tumorigenic settings by developing two g...
Source: The Biochemical Journal - October 31, 2023 Category: Biochemistry Authors: Tanner Wright Yalong Wang Sabrina A Stratton Manu Sebastian Bin Liu David G Johnson Mark T Bedford Source Type: research
Biochemical investigations of polyphenol degradation enzymes in the phototrophic bacterium Rubrivivax gelatinosus
Biochem J. 2023 Oct 30:BCJ20230387. doi: 10.1042/BCJ20230387. Online ahead of print.ABSTRACTPhloroglucinol (1,3,5-trihydroxybenzene) is an important intermediate in the degradation of flavonoids and tannins by anaerobic bacteria. Recent studies have shed light on the enzymatic mechanism of phloroglucinol degradation in butyrate-forming anaerobic bacteria, including environmental and intestinal bacteria such as Clostridium and Flavonifractor sp. Phloroglucinol degradation gene clusters have also been identified in other metabolically diverse bacteria, although the polyphenol metabolism of these microorganisms remain largely...
Source: The Biochemical Journal - October 30, 2023 Category: Biochemistry Authors: Yan Zhou Mengyu Cui Yifeng Wei Jason Tan Tong Li Xinan Jiao Source Type: research
Fluorescent biosensors illuminate the spatial regulation of cell signaling across scales
Biochem J. 2023 Oct 31;480(20):1693-1717. doi: 10.1042/BCJ20220223.ABSTRACTAs cell signaling research has advanced, it has become clearer that signal transduction has complex spatiotemporal regulation that goes beyond foundational linear transduction models. Several technologies have enabled these discoveries, including fluorescent biosensors designed to report live biochemical signaling events. As genetically encoded and live-cell compatible tools, fluorescent biosensors are well suited to address diverse cell signaling questions across different spatial scales of regulation. In this review, methods of examining spatial s...
Source: The Biochemical Journal - October 30, 2023 Category: Biochemistry Authors: Anne C Lyons Sohum Mehta Jin Zhang Source Type: research
Biochemical investigations of polyphenol degradation enzymes in the phototrophic bacterium Rubrivivax gelatinosus
Biochem J. 2023 Oct 30:BCJ20230387. doi: 10.1042/BCJ20230387. Online ahead of print.ABSTRACTPhloroglucinol (1,3,5-trihydroxybenzene) is an important intermediate in the degradation of flavonoids and tannins by anaerobic bacteria. Recent studies have shed light on the enzymatic mechanism of phloroglucinol degradation in butyrate-forming anaerobic bacteria, including environmental and intestinal bacteria such as Clostridium and Flavonifractor sp. Phloroglucinol degradation gene clusters have also been identified in other metabolically diverse bacteria, although the polyphenol metabolism of these microorganisms remain largely...
Source: The Biochemical Journal - October 30, 2023 Category: Biochemistry Authors: Yan Zhou Mengyu Cui Yifeng Wei Jason Tan Tong Li Xinan Jiao Source Type: research
Fluorescent biosensors illuminate the spatial regulation of cell signaling across scales
Biochem J. 2023 Oct 31;480(20):1693-1717. doi: 10.1042/BCJ20220223.ABSTRACTAs cell signaling research has advanced, it has become clearer that signal transduction has complex spatiotemporal regulation that goes beyond foundational linear transduction models. Several technologies have enabled these discoveries, including fluorescent biosensors designed to report live biochemical signaling events. As genetically encoded and live-cell compatible tools, fluorescent biosensors are well suited to address diverse cell signaling questions across different spatial scales of regulation. In this review, methods of examining spatial s...
Source: The Biochemical Journal - October 30, 2023 Category: Biochemistry Authors: Anne C Lyons Sohum Mehta Jin Zhang Source Type: research
PHF1 compartmentalizes PRC2 via phase separation
In this report, we demonstrate that a PCL protein named PHF1 forms phase-separated condensates at H3K27me3 loci that recruit PRC2. Combining cellular observation and biochemical reconstitution, we show that the N-terminal domains of PHF1 cooperatively mediate target recognition, the chromo-like domain recruits PRC2, and the intrinsically disordered region (IDR) drives phase separation. Moreover, we reveal that the condensates compartmentalize PRC2, DNA, and nucleosome arrays by phase separation. Luciferase reporter assays confirm that PHF1 phase separation promotes transcription repression, further supporting a role of the...
Source: The Biochemical Journal - October 27, 2023 Category: Biochemistry Authors: Genzhe Lu Pilong Li Source Type: research
PHF1 compartmentalizes PRC2 via phase separation
In this report, we demonstrate that a PCL protein named PHF1 forms phase-separated condensates at H3K27me3 loci that recruit PRC2. Combining cellular observation and biochemical reconstitution, we show that the N-terminal domains of PHF1 cooperatively mediate target recognition, the chromo-like domain recruits PRC2, and the intrinsically disordered region (IDR) drives phase separation. Moreover, we reveal that the condensates compartmentalize PRC2, DNA, and nucleosome arrays by phase separation. Luciferase reporter assays confirm that PHF1 phase separation promotes transcription repression, further supporting a role of the...
Source: The Biochemical Journal - October 27, 2023 Category: Biochemistry Authors: Genzhe Lu Pilong Li Source Type: research
PHF1 compartmentalizes PRC2 via phase separation
In this report, we demonstrate that a PCL protein named PHF1 forms phase-separated condensates at H3K27me3 loci that recruit PRC2. Combining cellular observation and biochemical reconstitution, we show that the N-terminal domains of PHF1 cooperatively mediate target recognition, the chromo-like domain recruits PRC2, and the intrinsically disordered region (IDR) drives phase separation. Moreover, we reveal that the condensates compartmentalize PRC2, DNA, and nucleosome arrays by phase separation. Luciferase reporter assays confirm that PHF1 phase separation promotes transcription repression, further supporting a role of the...
Source: The Biochemical Journal - October 27, 2023 Category: Biochemistry Authors: Genzhe Lu Pilong Li Source Type: research
Activating Mutations Drive Human MEK1 Kinase Using a Gear-Shifting Mechanism
Biochem J. 2023 Oct 23:BCJ20230281. doi: 10.1042/BCJ20230281. Online ahead of print.ABSTRACTThere is an unmet need to classify cancer-promoting kinase mutations in a mechanistically cognizant way. The challenge is to understand mutations stabilize different kinase configurations to alter function, and how this influences pathogenic potential of the kinase and its responses to therapeutic inhibitors. This goal is made more challenging by the complexity of the mutational landscape of diseases, and is further compounded by the conformational plasticity of each variant where multiple conformations co-exist. We focus here on th...
Source: The Biochemical Journal - October 23, 2023 Category: Biochemistry Authors: Keshav Patil Yiming Wang Zhangtao Chen Krishna Suresh Ravi Radhakrishnan Source Type: research
Catalysis of non-canonical protein ubiquitylation by the ARIH1 ubiquitin ligase
Biochem J. 2023 Oct 23:BCJ20230373. doi: 10.1042/BCJ20230373. Online ahead of print.ABSTRACTProtein ubiquitylation typically involves isopeptide bond formation between the C-terminus of ubiquitin to the side-chain amino group on Lys residues. However, several ubiquitin ligases (E3s) have recently been identified that ubiquitylate proteins on non-Lys residues. For instance, HOIL-1 belongs to the RING-in-between RING (RBR) class of E3s and has an established role in Ser ubiquitylation. Given the homology between HOIL-1 and ARIH1, an RBR E3 that functions with the large superfamily of cullin-RING E3 ligases (CRLs), a biochemi...
Source: The Biochemical Journal - October 23, 2023 Category: Biochemistry Authors: Nicholas Purser Ishita Tripathi-Giesgen Jerry Li Daniel C Scott Daniel Horn-Ghetko Kheewoong Baek Brenda A Schulman Arno F Alpi Gary Kleiger Source Type: research
Activating Mutations Drive Human MEK1 Kinase Using a Gear-Shifting Mechanism
Biochem J. 2023 Oct 23:BCJ20230281. doi: 10.1042/BCJ20230281. Online ahead of print.ABSTRACTThere is an unmet need to classify cancer-promoting kinase mutations in a mechanistically cognizant way. The challenge is to understand mutations stabilize different kinase configurations to alter function, and how this influences pathogenic potential of the kinase and its responses to therapeutic inhibitors. This goal is made more challenging by the complexity of the mutational landscape of diseases, and is further compounded by the conformational plasticity of each variant where multiple conformations co-exist. We focus here on th...
Source: The Biochemical Journal - October 23, 2023 Category: Biochemistry Authors: Keshav Patil Yiming Wang Zhangtao Chen Krishna Suresh Ravi Radhakrishnan Source Type: research
Catalysis of non-canonical protein ubiquitylation by the ARIH1 ubiquitin ligase
Biochem J. 2023 Oct 23:BCJ20230373. doi: 10.1042/BCJ20230373. Online ahead of print.ABSTRACTProtein ubiquitylation typically involves isopeptide bond formation between the C-terminus of ubiquitin to the side-chain amino group on Lys residues. However, several ubiquitin ligases (E3s) have recently been identified that ubiquitylate proteins on non-Lys residues. For instance, HOIL-1 belongs to the RING-in-between RING (RBR) class of E3s and has an established role in Ser ubiquitylation. Given the homology between HOIL-1 and ARIH1, an RBR E3 that functions with the large superfamily of cullin-RING E3 ligases (CRLs), a biochemi...
Source: The Biochemical Journal - October 23, 2023 Category: Biochemistry Authors: Nicholas Purser Ishita Tripathi-Giesgen Jerry Li Daniel C Scott Daniel Horn-Ghetko Kheewoong Baek Brenda A Schulman Arno F Alpi Gary Kleiger Source Type: research
Activating Mutations Drive Human MEK1 Kinase Using a Gear-Shifting Mechanism
Biochem J. 2023 Oct 23:BCJ20230281. doi: 10.1042/BCJ20230281. Online ahead of print.ABSTRACTThere is an unmet need to classify cancer-promoting kinase mutations in a mechanistically cognizant way. The challenge is to understand mutations stabilize different kinase configurations to alter function, and how this influences pathogenic potential of the kinase and its responses to therapeutic inhibitors. This goal is made more challenging by the complexity of the mutational landscape of diseases, and is further compounded by the conformational plasticity of each variant where multiple conformations co-exist. We focus here on th...
Source: The Biochemical Journal - October 23, 2023 Category: Biochemistry Authors: Keshav Patil Yiming Wang Zhangtao Chen Krishna Suresh Ravi Radhakrishnan Source Type: research
Catalysis of non-canonical protein ubiquitylation by the ARIH1 ubiquitin ligase
Biochem J. 2023 Oct 23:BCJ20230373. doi: 10.1042/BCJ20230373. Online ahead of print.ABSTRACTProtein ubiquitylation typically involves isopeptide bond formation between the C-terminus of ubiquitin to the side-chain amino group on Lys residues. However, several ubiquitin ligases (E3s) have recently been identified that ubiquitylate proteins on non-Lys residues. For instance, HOIL-1 belongs to the RING-in-between RING (RBR) class of E3s and has an established role in Ser ubiquitylation. Given the homology between HOIL-1 and ARIH1, an RBR E3 that functions with the large superfamily of cullin-RING E3 ligases (CRLs), a biochemi...
Source: The Biochemical Journal - October 23, 2023 Category: Biochemistry Authors: Nicholas Purser Ishita Tripathi-Giesgen Jerry Li Daniel C Scott Daniel Horn-Ghetko Kheewoong Baek Brenda A Schulman Arno F Alpi Gary Kleiger Source Type: research
Activating Mutations Drive Human MEK1 Kinase Using a Gear-Shifting Mechanism
Biochem J. 2023 Oct 23:BCJ20230281. doi: 10.1042/BCJ20230281. Online ahead of print.ABSTRACTThere is an unmet need to classify cancer-promoting kinase mutations in a mechanistically cognizant way. The challenge is to understand mutations stabilize different kinase configurations to alter function, and how this influences pathogenic potential of the kinase and its responses to therapeutic inhibitors. This goal is made more challenging by the complexity of the mutational landscape of diseases, and is further compounded by the conformational plasticity of each variant where multiple conformations co-exist. We focus here on th...
Source: The Biochemical Journal - October 23, 2023 Category: Biochemistry Authors: Keshav Patil Yiming Wang Zhangtao Chen Krishna Suresh Ravi Radhakrishnan Source Type: research
