Correction for Tian et al.,
            <i>BRCA1</i>
            promotes the ubiquitination of PCNA and recruitment of translesion polymerases in response to replication blockade

Tian, Fen; Sharma, Shilpy; Zou, Jianqiu; Lin, Shiaw Yih; Wang, Bin; Rezvani, Khosrow; Wang, Hongmin; Parvin, Jeffrey D.; Ludwig, Thomas; Canman, Christine E.; Zhang, Dong

doi:10.1073/pnas.1316463110

“…Calpain cleavage was discussed above. Citrullination of R3 and R5 residues within GSK3β is important for nuclear localization (Stadler et al, 2013). However, we observed that mTORC1 controls both GSK3α and GSK3β nuclear localization, and these two GSK3 paralogs differ at their N-terminus within the region of GSK3β that are expected to undergo citrullination.…”

Section: Specific Amino Acids Acutely Promote Gsk3 Nuclear Exportmentioning

confidence: 62%

“…Other than phosphorylation, other modifications reported for GSK3β include citrullination (Stadler et al, 2013) and calpain cleavage (Goñi-Oliver et al, 2007). Calpain cleavage was discussed above.…”

Section: Specific Amino Acids Acutely Promote Gsk3 Nuclear Exportmentioning

confidence: 96%

“…receives. Two post translational modifications, citrunillation of GSK3β(Stadler et al, 2013) and calpain cleavage of GSK3(Goñi-Oliver et al, 2007), both promote GSK3 translocation from the cytosolic to the nucleus (Fig.1.17). During different cellular events, heat shock(Bijur and Jope, 2001), PI3K-Akt suppression in embryonic stem cells (Dalton and, in S phase of the cell cycle(Diehl et al, 1998), and engagement of cell senescence(Zmijewski and Jope, 2004), GSK3 undergoes nuclear translocation, suggesting a regulated alteration in the function of GSK3 under these conditions.…”

mentioning

confidence: 99%

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Mitogenic and Metabolic signals regulate mTOR complex 1 function to control GSK3β nuclear program

Bautista¹

2021

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0

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Mitogenic and metabolic signalling are two cell pathways that control different aspects of cellular physiology including, growth, proliferation, metabolism, and transcription. Mitogenic signalling involves mitogens and growth factors to stimulate various receptor signalling pathways such as epidermal growth factor receptor (EGFR), while metabolic signalling involves proteins that sense changes in abundance of specific nutrients or metabolites such as amino acids and ATP. Here, I have uncovered that EGFR signalling is controlled by clathrin nanodomains at the plasma membrane, yet this requirement for clathrin does not reflect a role for receptor internalization in EGFR signalling. Specifically, I found that clathrin is required for activation of the key signaling intermediate Akt by EGFR upon EGF stimulation. Furthermore, I have also resolved a series of signals including Phospholipase C γ1 (PLCγ1) that may control EGF stimulated Akt activation by modulating the assembly of clathrin into plasma membrane nanodomains. These findings suggest that clathrin nanodomains at the plasma membrane are important for controlling EGFR signalling, thus impacting mitogenic signaling. A downstream signalling pathway controlled by Akt is the Glycogen synthase kinase 3 (GSK3) pathway. GSK3 phosphorylates and thereby regulates a wide range of protein substrates involved in diverse cellular functions. Some GSK3 substrates, such as c-Myc and Snail, are nuclear transcription factors, suggesting the possibility that GSK3 function is controlled through regulation of its nuclear localization. I found that perturbations in mTOR complex 1 (mTORC1) leads to partial redistribution of GSK3 from the cytosol to the nucleus and to a GSK3 dependent reduction of the levels of both c-Myc and Snail. In addition to conditional nuclear localization, GSK3 was also detected on several distinct endomembrane compartments, including lysosomes. Consistently, disruption of various aspects of the function and regulation late endosomes/lysosomes resulted in perturbation of GSK3 nucleocytoplasmic shuttling and activity. Furthermore, I found that DEPDC5, a subunit of the lysosomal amino-acid sensing GATOR1 complex, controls amino acid sensing mechanisms to regulate GSK3 nucleocytoplasmic shuttling. These findings uncover a new signalling axis that is controlled by specific aspects of both mitogenic and metabolic signalling, which may interface with the nucleus to reprogram transcriptional cellular networks for growth and proliferation. Understanding how mTORC1- GSK3 signalling impacts transcriptional networks may be an important target for different therapies and treatments against diverse forms of cancer.

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“…3A,B), with the intensity of fluorescent lignin at the cortex-facing cell wall being consistently more prominent than the one at the pericycle-facing one. This pattern of ectopic lignification is precisely re-iterating the compensatory lignification observed in many other CS-defective mutants (31,33,39,40). It is known to depend on SCHENGEN (SGN) pathway activation and eventually leads to an alternative, though significantly delayed, formation of an apoplastic diffusion barrier in CS mutants.…”

Section: A Per3 9 39 72 64 Quintuple Mutant Is Devoid Of Casparian Stmentioning

confidence: 63%

“…1E). CASPs co-localize with other cell wall proteins at the CS, such as PEROXIDASE 64 (PER64) and ENHANCED SUBERIN 1 (ESB1), both involved in CS formation (2,33). Thus, laccases and peroxidases localize to the same cell wall domain in the endodermis.…”

Section: Protein Fusions Of Lac1 Lac3 Lac5 and Lac13 Accumulate At mentioning

confidence: 99%

High-order mutants reveal an essential requirement for peroxidases but not laccases in Casparian strip lignification

Rojas-Murcia

¹

,

Hématy

²

,

Lee

³

et al. 2020

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The invention of lignin has been at the heart of plants' capacity to colonize land, allowing them to grow tall, transport water within their bodies and protect themselves against various stresses.Consequently, this polyphenolic polymer, that impregnates the cellulosic plant cell walls, now represents the second most abundant polymer on Earth, after cellulose itself. Yet, despite its great physiological, ecological and economical importance, our knowledge of lignin biosynthesis in vivo, especially the crucial last steps of polymerization within the cell wall, remains vague. Specifically, the respective roles and importance of the two main polymerizing enzymes classes, laccases and peroxidases have remained obscure. One reason for this lies in

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Mitogenic and Metabolic signals regulate mTOR complex 1 function to control GSK3β nuclear program

Bautista¹

2021

Preprint

0

View full text Add to dashboard Cite

Mitogenic and metabolic signalling are two cell pathways that control different aspects of cellular physiology including, growth, proliferation, metabolism, and transcription. Mitogenic signalling involves mitogens and growth factors to stimulate various receptor signalling pathways such as epidermal growth factor receptor (EGFR), while metabolic signalling involves proteins that sense changes in abundance of specific nutrients or metabolites such as amino acids and ATP. Here, I have uncovered that EGFR signalling is controlled by clathrin nanodomains at the plasma membrane, yet this requirement for clathrin does not reflect a role for receptor internalization in EGFR signalling. Specifically, I found that clathrin is required for activation of the key signaling intermediate Akt by EGFR upon EGF stimulation. Furthermore, I have also resolved a series of signals including Phospholipase C γ1 (PLCγ1) that may control EGF stimulated Akt activation by modulating the assembly of clathrin into plasma membrane nanodomains. These findings suggest that clathrin nanodomains at the plasma membrane are important for controlling EGFR signalling, thus impacting mitogenic signaling. A downstream signalling pathway controlled by Akt is the Glycogen synthase kinase 3 (GSK3) pathway. GSK3 phosphorylates and thereby regulates a wide range of protein substrates involved in diverse cellular functions. Some GSK3 substrates, such as c-Myc and Snail, are nuclear transcription factors, suggesting the possibility that GSK3 function is controlled through regulation of its nuclear localization. I found that perturbations in mTOR complex 1 (mTORC1) leads to partial redistribution of GSK3 from the cytosol to the nucleus and to a GSK3 dependent reduction of the levels of both c-Myc and Snail. In addition to conditional nuclear localization, GSK3 was also detected on several distinct endomembrane compartments, including lysosomes. Consistently, disruption of various aspects of the function and regulation late endosomes/lysosomes resulted in perturbation of GSK3 nucleocytoplasmic shuttling and activity. Furthermore, I found that DEPDC5, a subunit of the lysosomal amino-acid sensing GATOR1 complex, controls amino acid sensing mechanisms to regulate GSK3 nucleocytoplasmic shuttling. These findings uncover a new signalling axis that is controlled by specific aspects of both mitogenic and metabolic signalling, which may interface with the nucleus to reprogram transcriptional cellular networks for growth and proliferation. Understanding how mTORC1- GSK3 signalling impacts transcriptional networks may be an important target for different therapies and treatments against diverse forms of cancer.

show abstract

Correction for Tian et al., BRCA1 promotes the ubiquitination of PCNA and recruitment of translesion polymerases in response to replication blockade

Abstract: a 41. Pathania S, et al. (2011) BRCA1 is required for postreplication repair after UV-induced DNA damage. Mol Cell 44(2):235-251.

Cited by 3 publications

References 1 publication

Mitogenic and Metabolic signals regulate mTOR complex 1 function to control GSK3β nuclear program

Mitogenic and Metabolic signals regulate mTOR complex 1 function to control GSK3β nuclear program

High-order mutants reveal an essential requirement for peroxidases but not laccases in Casparian strip lignification

Mitogenic and Metabolic signals regulate mTOR complex 1 function to control GSK3β nuclear program

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