Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2 α phosphorylation
Biochem J. 2024 Mar 5:BCJ20220531. doi: 10.1042/BCJ20220531. Online ahead of print.ABSTRACTThe 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 cop...
Source: The Biochemical Journal - March 5, 2024 Category: Biochemistry Authors: Renuka Shanmugam Reuben Anderson Anja H Schiemann Evelyn Sattlegger Source Type: research

Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2 α phosphorylation
Biochem J. 2024 Mar 5:BCJ20220531. doi: 10.1042/BCJ20220531. Online ahead of print.ABSTRACTThe 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 cop...
Source: The Biochemical Journal - March 5, 2024 Category: Biochemistry Authors: Renuka Shanmugam Reuben Anderson Anja H Schiemann Evelyn Sattlegger Source Type: research

Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2 α phosphorylation
Biochem J. 2024 Mar 5:BCJ20220531. doi: 10.1042/BCJ20220531. Online ahead of print.ABSTRACTThe 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 cop...
Source: The Biochemical Journal - March 5, 2024 Category: Biochemistry Authors: Renuka Shanmugam Reuben Anderson Anja H Schiemann Evelyn Sattlegger Source Type: research

Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2 α phosphorylation
Biochem J. 2024 Mar 5:BCJ20220531. doi: 10.1042/BCJ20220531. Online ahead of print.ABSTRACTThe 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 cop...
Source: The Biochemical Journal - March 5, 2024 Category: Biochemistry Authors: Renuka Shanmugam Reuben Anderson Anja H Schiemann Evelyn Sattlegger Source Type: research

Dynamic interactions between SPX proteins, the ubiquitination machinery, and signalling molecules for stress adaptation at a whole-plant level
Biochem J. 2024 Mar 6;481(5):363-385. doi: 10.1042/BCJ20230163.ABSTRACTThe plant macronutrient phosphorus is a scarce resource and plant-available phosphate is limiting in most soil types. Generally, a gene regulatory module called the phosphate starvation response (PSR) enables efficient phosphate acquisition by roots and translocation to other organs. Plants growing on moderate to nutrient-rich soils need to co-ordinate availability of different nutrients and repress the highly efficient PSR to adjust phosphate acquisition to the availability of other macro- and micronutrients, and in particular nitrogen. PSR repression ...
Source: The Biochemical Journal - February 29, 2024 Category: Biochemistry Authors: Emma Collins Huixia Shou Chuanzao Mao James Whelan Ricarda Jost Source Type: research

Dynamic interactions between SPX proteins, the ubiquitination machinery, and signalling molecules for stress adaptation at a whole-plant level
Biochem J. 2024 Mar 6;481(5):363-385. doi: 10.1042/BCJ20230163.ABSTRACTThe plant macronutrient phosphorus is a scarce resource and plant-available phosphate is limiting in most soil types. Generally, a gene regulatory module called the phosphate starvation response (PSR) enables efficient phosphate acquisition by roots and translocation to other organs. Plants growing on moderate to nutrient-rich soils need to co-ordinate availability of different nutrients and repress the highly efficient PSR to adjust phosphate acquisition to the availability of other macro- and micronutrients, and in particular nitrogen. PSR repression ...
Source: The Biochemical Journal - February 29, 2024 Category: Biochemistry Authors: Emma Collins Huixia Shou Chuanzao Mao James Whelan Ricarda Jost Source Type: research

Dynamic interactions between SPX proteins, the ubiquitination machinery, and signalling molecules for stress adaptation at a whole-plant level
Biochem J. 2024 Mar 6;481(5):363-385. doi: 10.1042/BCJ20230163.ABSTRACTThe plant macronutrient phosphorus is a scarce resource and plant-available phosphate is limiting in most soil types. Generally, a gene regulatory module called the phosphate starvation response (PSR) enables efficient phosphate acquisition by roots and translocation to other organs. Plants growing on moderate to nutrient-rich soils need to co-ordinate availability of different nutrients and repress the highly efficient PSR to adjust phosphate acquisition to the availability of other macro- and micronutrients, and in particular nitrogen. PSR repression ...
Source: The Biochemical Journal - February 29, 2024 Category: Biochemistry Authors: Emma Collins Huixia Shou Chuanzao Mao James Whelan Ricarda Jost Source Type: research

Dynamic interactions between SPX proteins, the ubiquitination machinery, and signalling molecules for stress adaptation at a whole-plant level
Biochem J. 2024 Mar 6;481(5):363-385. doi: 10.1042/BCJ20230163.ABSTRACTThe plant macronutrient phosphorus is a scarce resource and plant-available phosphate is limiting in most soil types. Generally, a gene regulatory module called the phosphate starvation response (PSR) enables efficient phosphate acquisition by roots and translocation to other organs. Plants growing on moderate to nutrient-rich soils need to co-ordinate availability of different nutrients and repress the highly efficient PSR to adjust phosphate acquisition to the availability of other macro- and micronutrients, and in particular nitrogen. PSR repression ...
Source: The Biochemical Journal - February 29, 2024 Category: Biochemistry Authors: Emma Collins Huixia Shou Chuanzao Mao James Whelan Ricarda Jost Source Type: research

Cardiomyocyte-specific deletion of GCN5L1 reduces lysine acetylation and attenuates diastolic dysfunction in aged mice by improving cardiac fatty acid oxidation
Biochem J. 2024 Feb 23:BCJ20230421. doi: 10.1042/BCJ20230421. Online ahead of print.ABSTRACTCardiac mitochondrial dysfunction is a critical contributor to the pathogenesis of aging and many age-related conditions. As such, complete control of mitochondrial function is critical to maintain cardiac efficiency in the aged heart. Lysine acetylation is a reversible post-translational modification shown to regulate several mitochondrial metabolic and biochemical processes. In the present study, we investigated how mitochondrial lysine acetylation regulates fatty acid oxidation and cardiac function in the aged heart. We found a s...
Source: The Biochemical Journal - February 23, 2024 Category: Biochemistry Authors: Jackson E Stewart Jenna M Crawford William E Mullen Angelica Jacques Michael W Stoner Iain Scott Dharendra Thapa Source Type: research

Cardiomyocyte-specific deletion of GCN5L1 reduces lysine acetylation and attenuates diastolic dysfunction in aged mice by improving cardiac fatty acid oxidation
Biochem J. 2024 Feb 23:BCJ20230421. doi: 10.1042/BCJ20230421. Online ahead of print.ABSTRACTCardiac mitochondrial dysfunction is a critical contributor to the pathogenesis of aging and many age-related conditions. As such, complete control of mitochondrial function is critical to maintain cardiac efficiency in the aged heart. Lysine acetylation is a reversible post-translational modification shown to regulate several mitochondrial metabolic and biochemical processes. In the present study, we investigated how mitochondrial lysine acetylation regulates fatty acid oxidation and cardiac function in the aged heart. We found a s...
Source: The Biochemical Journal - February 23, 2024 Category: Biochemistry Authors: Jackson E Stewart Jenna M Crawford William E Mullen Angelica Jacques Michael W Stoner Iain Scott Dharendra Thapa Source Type: research

Cardiomyocyte-specific deletion of GCN5L1 reduces lysine acetylation and attenuates diastolic dysfunction in aged mice by improving cardiac fatty acid oxidation
Biochem J. 2024 Feb 23:BCJ20230421. doi: 10.1042/BCJ20230421. Online ahead of print.ABSTRACTCardiac mitochondrial dysfunction is a critical contributor to the pathogenesis of aging and many age-related conditions. As such, complete control of mitochondrial function is critical to maintain cardiac efficiency in the aged heart. Lysine acetylation is a reversible post-translational modification shown to regulate several mitochondrial metabolic and biochemical processes. In the present study, we investigated how mitochondrial lysine acetylation regulates fatty acid oxidation and cardiac function in the aged heart. We found a s...
Source: The Biochemical Journal - February 23, 2024 Category: Biochemistry Authors: Jackson E Stewart Jenna M Crawford William E Mullen Angelica Jacques Michael W Stoner Iain Scott Dharendra Thapa Source Type: research

Cardiomyocyte-specific deletion of GCN5L1 reduces lysine acetylation and attenuates diastolic dysfunction in aged mice by improving cardiac fatty acid oxidation
Biochem J. 2024 Feb 23:BCJ20230421. doi: 10.1042/BCJ20230421. Online ahead of print.ABSTRACTCardiac mitochondrial dysfunction is a critical contributor to the pathogenesis of aging and many age-related conditions. As such, complete control of mitochondrial function is critical to maintain cardiac efficiency in the aged heart. Lysine acetylation is a reversible post-translational modification shown to regulate several mitochondrial metabolic and biochemical processes. In the present study, we investigated how mitochondrial lysine acetylation regulates fatty acid oxidation and cardiac function in the aged heart. We found a s...
Source: The Biochemical Journal - February 23, 2024 Category: Biochemistry Authors: Jackson E Stewart Jenna M Crawford William E Mullen Angelica Jacques Michael W Stoner Iain Scott Dharendra Thapa Source Type: research

Cardiomyocyte-specific deletion of GCN5L1 reduces lysine acetylation and attenuates diastolic dysfunction in aged mice by improving cardiac fatty acid oxidation
Biochem J. 2024 Feb 23:BCJ20230421. doi: 10.1042/BCJ20230421. Online ahead of print.ABSTRACTCardiac mitochondrial dysfunction is a critical contributor to the pathogenesis of aging and many age-related conditions. As such, complete control of mitochondrial function is critical to maintain cardiac efficiency in the aged heart. Lysine acetylation is a reversible post-translational modification shown to regulate several mitochondrial metabolic and biochemical processes. In the present study, we investigated how mitochondrial lysine acetylation regulates fatty acid oxidation and cardiac function in the aged heart. We found a s...
Source: The Biochemical Journal - February 23, 2024 Category: Biochemistry Authors: Jackson E Stewart Jenna M Crawford William E Mullen Angelica Jacques Michael W Stoner Iain Scott Dharendra Thapa Source Type: research

Reporter cell lines to screen for inhibitors or regulators of the KRAS-RAF-MEK1/2-ERK1/2 pathway
Biochem J. 2024 Feb 21:BCJ20240015. doi: 10.1042/BCJ20240015. Online ahead of print.ABSTRACTThe RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is activated in cancer due to mutations in RAS proteins (especially KRAS), BRAF, CRAF, MEK1 and MEK2. Whilst inhibitors of KRASG12C (lung adenocarcinoma) and BRAF and MEK1/2 (melanoma and colorectal cancer) are clinically approved, acquired resistance remains a problem. Consequently, the search for new inhibitors (especially of RAS proteins), new inhibitor modalities and regulators of this pathway, which may be new drug targets, continues and increasingly involves cell-based scr...
Source: The Biochemical Journal - February 21, 2024 Category: Biochemistry Authors: Laura Weatherdon Kate Stuart Megan A Cassidy Alberto Moreno de la G ándara Hanneke Okkenhaug Markus Muellener Grahame Mckenzie Simon J Cook Rebecca Gilley Source Type: research

Reporter cell lines to screen for inhibitors or regulators of the KRAS-RAF-MEK1/2-ERK1/2 pathway
Biochem J. 2024 Feb 21:BCJ20240015. doi: 10.1042/BCJ20240015. Online ahead of print.ABSTRACTThe RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is activated in cancer due to mutations in RAS proteins (especially KRAS), BRAF, CRAF, MEK1 and MEK2. Whilst inhibitors of KRASG12C (lung adenocarcinoma) and BRAF and MEK1/2 (melanoma and colorectal cancer) are clinically approved, acquired resistance remains a problem. Consequently, the search for new inhibitors (especially of RAS proteins), new inhibitor modalities and regulators of this pathway, which may be new drug targets, continues and increasingly involves cell-based scr...
Source: The Biochemical Journal - February 21, 2024 Category: Biochemistry Authors: Laura Weatherdon Kate Stuart Megan A Cassidy Alberto Moreno de la G ándara Hanneke Okkenhaug Markus Muellener Grahame Mckenzie Simon J Cook Rebecca Gilley Source Type: research