Interactions of mitochondrial and skeletal muscle biology in mitochondrial myopathy
Biochem J. 2023 Nov 15;480(21):1767-1789. doi: 10.1042/BCJ20220233.ABSTRACTMitochondrial dysfunction in skeletal muscle fibres occurs with both healthy aging and a range of neuromuscular diseases. The impact of mitochondrial dysfunction in skeletal muscle and the way muscle fibres adapt to this dysfunction is important to understand disease mechanisms and to develop therapeutic interventions. Furthermore, interactions between mitochondrial dysfunction and skeletal muscle biology, in mitochondrial myopathy, likely have important implications for normal muscle function and physiology. In this review, we will try to give an o...
Source: The Biochemical Journal - November 15, 2023 Category: Biochemistry Authors: Valeria Di Leo Tiago M Bernardino Gomes Amy E Vincent Source Type: research

Frequent loss-of-function mutations in the AMPK- α2 catalytic subunit suggest a tumour suppressor role in human skin cancers
Biochem J. 2022 Nov 14:BCJ20230380. doi: 10.1042/BCJ20230380. Online ahead of print.ABSTRACTThe AMP-activated protein kinase (AMPK) is a sensor of cellular energy status activated by increases in AMP or ADP relative to ATP. Once activated, it phosphorylates targets that promote ATP-generating catabolic pathways or inhibit ATP-consuming anabolic pathways, helping to restore cellular energy balance. Analysis of human cancer genome studies reveals that the PRKAA2 gene (encoding the α2 isoform of the catalytic subunit) is often subject to mis-sense mutations in cancer, particularly in melanoma and non-melanoma skin cancers, w...
Source: The Biochemical Journal - November 14, 2023 Category: Biochemistry Authors: D Grahame Hardie Fiona A Ross Simon A Hawley Fiona M Russell Nicola Goodman Source Type: research

Frequent loss-of-function mutations in the AMPK- α2 catalytic subunit suggest a tumour suppressor role in human skin cancers
Biochem J. 2022 Nov 14:BCJ20230380. doi: 10.1042/BCJ20230380. Online ahead of print.ABSTRACTThe AMP-activated protein kinase (AMPK) is a sensor of cellular energy status activated by increases in AMP or ADP relative to ATP. Once activated, it phosphorylates targets that promote ATP-generating catabolic pathways or inhibit ATP-consuming anabolic pathways, helping to restore cellular energy balance. Analysis of human cancer genome studies reveals that the PRKAA2 gene (encoding the α2 isoform of the catalytic subunit) is often subject to mis-sense mutations in cancer, particularly in melanoma and non-melanoma skin cancers, w...
Source: The Biochemical Journal - November 14, 2023 Category: Biochemistry Authors: D Grahame Hardie Fiona A Ross Simon A Hawley Fiona M Russell Nicola Goodman Source Type: research

Elucidating the interaction of C-terminal domain of Vaccinia-Related Kinase2A(VRK2A) with B-cell lymphoma-extra Large(Bcl-xL) to decipher its anti-apoptotic role in cancer
Biochem J. 2023 Nov 9:BCJ20230349. doi: 10.1042/BCJ20230349. Online ahead of print.ABSTRACTVaccinia-Related Kinase 2 (VRK2) is an anti-apoptotic Ser/Thr kinase that enhances drug sensitivity in cancer cells. This protein exists in two isoforms: VRK2A, the longer variant, and VRK2B, which lacks the C-terminal region and transmembrane domain. While the therapeutic importance of VRK2 family proteins is known, the specific roles of VRK2A and its interplay with apoptotic regulator Bcl-xL (B-cell lymphoma-extra Large) remain elusive. Bcl-xL regulates cell death by interacting with BAX (B-cell lymphoma-2 Associated X-protein), co...
Source: The Biochemical Journal - November 9, 2023 Category: Biochemistry Authors: Rashmi Puja Shubhankar Dutta Kakoli Bose Source Type: research

Elucidating the interaction of C-terminal domain of Vaccinia-Related Kinase2A(VRK2A) with B-cell lymphoma-extra Large(Bcl-xL) to decipher its anti-apoptotic role in cancer
Biochem J. 2023 Nov 9:BCJ20230349. doi: 10.1042/BCJ20230349. Online ahead of print.ABSTRACTVaccinia-Related Kinase 2 (VRK2) is an anti-apoptotic Ser/Thr kinase that enhances drug sensitivity in cancer cells. This protein exists in two isoforms: VRK2A, the longer variant, and VRK2B, which lacks the C-terminal region and transmembrane domain. While the therapeutic importance of VRK2 family proteins is known, the specific roles of VRK2A and its interplay with apoptotic regulator Bcl-xL (B-cell lymphoma-extra Large) remain elusive. Bcl-xL regulates cell death by interacting with BAX (B-cell lymphoma-2 Associated X-protein), co...
Source: The Biochemical Journal - November 9, 2023 Category: Biochemistry Authors: Rashmi Puja Shubhankar Dutta Kakoli Bose Source Type: research

Elucidating the interaction of C-terminal domain of Vaccinia-Related Kinase2A(VRK2A) with B-cell lymphoma-extra Large(Bcl-xL) to decipher its anti-apoptotic role in cancer
Biochem J. 2023 Nov 9:BCJ20230349. doi: 10.1042/BCJ20230349. Online ahead of print.ABSTRACTVaccinia-Related Kinase 2 (VRK2) is an anti-apoptotic Ser/Thr kinase that enhances drug sensitivity in cancer cells. This protein exists in two isoforms: VRK2A, the longer variant, and VRK2B, which lacks the C-terminal region and transmembrane domain. While the therapeutic importance of VRK2 family proteins is known, the specific roles of VRK2A and its interplay with apoptotic regulator Bcl-xL (B-cell lymphoma-extra Large) remain elusive. Bcl-xL regulates cell death by interacting with BAX (B-cell lymphoma-2 Associated X-protein), co...
Source: The Biochemical Journal - November 9, 2023 Category: Biochemistry Authors: Rashmi Puja Shubhankar Dutta Kakoli Bose Source Type: research

Elucidating the interaction of C-terminal domain of Vaccinia-Related Kinase2A(VRK2A) with B-cell lymphoma-extra Large(Bcl-xL) to decipher its anti-apoptotic role in cancer
Biochem J. 2023 Nov 9:BCJ20230349. doi: 10.1042/BCJ20230349. Online ahead of print.ABSTRACTVaccinia-Related Kinase 2 (VRK2) is an anti-apoptotic Ser/Thr kinase that enhances drug sensitivity in cancer cells. This protein exists in two isoforms: VRK2A, the longer variant, and VRK2B, which lacks the C-terminal region and transmembrane domain. While the therapeutic importance of VRK2 family proteins is known, the specific roles of VRK2A and its interplay with apoptotic regulator Bcl-xL (B-cell lymphoma-extra Large) remain elusive. Bcl-xL regulates cell death by interacting with BAX (B-cell lymphoma-2 Associated X-protein), co...
Source: The Biochemical Journal - November 9, 2023 Category: Biochemistry Authors: Rashmi Puja Shubhankar Dutta Kakoli Bose Source Type: research

Elucidating the interaction of C-terminal domain of Vaccinia-Related Kinase2A(VRK2A) with B-cell lymphoma-extra Large(Bcl-xL) to decipher its anti-apoptotic role in cancer
Biochem J. 2023 Nov 9:BCJ20230349. doi: 10.1042/BCJ20230349. Online ahead of print.ABSTRACTVaccinia-Related Kinase 2 (VRK2) is an anti-apoptotic Ser/Thr kinase that enhances drug sensitivity in cancer cells. This protein exists in two isoforms: VRK2A, the longer variant, and VRK2B, which lacks the C-terminal region and transmembrane domain. While the therapeutic importance of VRK2 family proteins is known, the specific roles of VRK2A and its interplay with apoptotic regulator Bcl-xL (B-cell lymphoma-extra Large) remain elusive. Bcl-xL regulates cell death by interacting with BAX (B-cell lymphoma-2 Associated X-protein), co...
Source: The Biochemical Journal - November 9, 2023 Category: Biochemistry Authors: Rashmi Puja Shubhankar Dutta Kakoli Bose Source Type: research

Targeting bacterial degradation machinery as an antibacterial strategy
Biochem J. 2023 Nov 15;480(21):1719-1731. doi: 10.1042/BCJ20230191.ABSTRACTThe exploitation of a cell's natural degradation machinery for therapeutic purposes is an exciting research area in its infancy with respect to bacteria. Here, we review current strategies targeting the ClpCP system, which is a proteolytic degradation complex essential in the biology of many bacterial species of scientific interest. Strategies include using natural product antibiotics or acyldepsipeptides to initiate the up- or down-regulation of ClpCP activity. We also examine exciting recent forays into BacPROTACs to trigger the degradation of spe...
Source: The Biochemical Journal - November 2, 2023 Category: Biochemistry Authors: Radoslav Petkov Amy H Camp Rivka L Isaacson James H Torpey Source Type: research

Targeting bacterial degradation machinery as an antibacterial strategy
Biochem J. 2023 Nov 15;480(21):1719-1731. doi: 10.1042/BCJ20230191.ABSTRACTThe exploitation of a cell's natural degradation machinery for therapeutic purposes is an exciting research area in its infancy with respect to bacteria. Here, we review current strategies targeting the ClpCP system, which is a proteolytic degradation complex essential in the biology of many bacterial species of scientific interest. Strategies include using natural product antibiotics or acyldepsipeptides to initiate the up- or down-regulation of ClpCP activity. We also examine exciting recent forays into BacPROTACs to trigger the degradation of spe...
Source: The Biochemical Journal - November 2, 2023 Category: Biochemistry Authors: Radoslav Petkov Amy H Camp Rivka L Isaacson James H Torpey Source Type: research

Targeting bacterial degradation machinery as an antibacterial strategy
Biochem J. 2023 Nov 15;480(21):1719-1731. doi: 10.1042/BCJ20230191.ABSTRACTThe exploitation of a cell's natural degradation machinery for therapeutic purposes is an exciting research area in its infancy with respect to bacteria. Here, we review current strategies targeting the ClpCP system, which is a proteolytic degradation complex essential in the biology of many bacterial species of scientific interest. Strategies include using natural product antibiotics or acyldepsipeptides to initiate the up- or down-regulation of ClpCP activity. We also examine exciting recent forays into BacPROTACs to trigger the degradation of spe...
Source: The Biochemical Journal - November 2, 2023 Category: Biochemistry Authors: Radoslav Petkov Amy H Camp Rivka L Isaacson James H Torpey Source Type: research

Targeting bacterial degradation machinery as an antibacterial strategy
Biochem J. 2023 Nov 15;480(21):1719-1731. doi: 10.1042/BCJ20230191.ABSTRACTThe exploitation of a cell's natural degradation machinery for therapeutic purposes is an exciting research area in its infancy with respect to bacteria. Here, we review current strategies targeting the ClpCP system, which is a proteolytic degradation complex essential in the biology of many bacterial species of scientific interest. Strategies include using natural product antibiotics or acyldepsipeptides to initiate the up- or down-regulation of ClpCP activity. We also examine exciting recent forays into BacPROTACs to trigger the degradation of spe...
Source: The Biochemical Journal - November 2, 2023 Category: Biochemistry Authors: Radoslav Petkov Amy H Camp Rivka L Isaacson James H Torpey Source Type: research

Targeting bacterial degradation machinery as an antibacterial strategy
Biochem J. 2023 Nov 15;480(21):1719-1731. doi: 10.1042/BCJ20230191.ABSTRACTThe exploitation of a cell's natural degradation machinery for therapeutic purposes is an exciting research area in its infancy with respect to bacteria. Here, we review current strategies targeting the ClpCP system, which is a proteolytic degradation complex essential in the biology of many bacterial species of scientific interest. Strategies include using natural product antibiotics or acyldepsipeptides to initiate the up- or down-regulation of ClpCP activity. We also examine exciting recent forays into BacPROTACs to trigger the degradation of spe...
Source: The Biochemical Journal - November 2, 2023 Category: Biochemistry Authors: Radoslav Petkov Amy H Camp Rivka L Isaacson James H Torpey Source Type: research

Targeting bacterial degradation machinery as an antibacterial strategy
Biochem J. 2023 Nov 15;480(21):1719-1731. doi: 10.1042/BCJ20230191.ABSTRACTThe exploitation of a cell's natural degradation machinery for therapeutic purposes is an exciting research area in its infancy with respect to bacteria. Here, we review current strategies targeting the ClpCP system, which is a proteolytic degradation complex essential in the biology of many bacterial species of scientific interest. Strategies include using natural product antibiotics or acyldepsipeptides to initiate the up- or down-regulation of ClpCP activity. We also examine exciting recent forays into BacPROTACs to trigger the degradation of spe...
Source: The Biochemical Journal - November 2, 2023 Category: Biochemistry Authors: Radoslav Petkov Amy H Camp Rivka L Isaacson James H Torpey Source Type: research

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