REPTOR and REPTOR-BP Regulate Organismal Metabolism and Transcription Downstream of TORC1

Tiebe, Marcel; Lutz, Martina S.; Garza, Adriana De La; Buechling, Tina; Boutros, Michael; Teleman, Aurelio A.

doi:10.1016/j.devcel.2015.03.013

Cited by 93 publications

(156 citation statements)

References 54 publications

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“…Another novel mTORC1 substrate discovered recently is the phosphatidylinositol-5-phosphate 4-kinase γ (PIP4Kγ) (Mackey et al, 2014). Finally, a major new transcriptional effector of TORC1 signaling was identified this year in Drosophila melanogaster , REPTOR (Tiebe et al, 2015). Much like FOXO, REPTOR is phosphorylated by TORC1 and thus sequestered in the cytoplasm by a 14-3-3 protein.…”

Section: Regulation Of Mtorc1 and Mtorc2 By Nutrient And Endocrine Simentioning

confidence: 99%

“…Much like FOXO, REPTOR is phosphorylated by TORC1 and thus sequestered in the cytoplasm by a 14-3-3 protein. Upon TORC1 inhibition, REPTOR is liberated by a phosphatase and translocates to the nucleus, where it binds target genes together with another protein, REPTOR-BP (Tiebe et al, 2015). Mammalian equivalents of REPTOR and REPTOR-BP have not yet been characterized, but Crebrf and Crebl2 are homologous human proteins (Tiebe et al, 2015).…”

Section: Regulation Of Mtorc1 and Mtorc2 By Nutrient And Endocrine Simentioning

confidence: 99%

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The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging

2016

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Summary Since the discovery that rapamycin, a small molecule inhibitor of the protein kinase mTOR (mechanistic Target Of Rapamycin), can extend the lifespan of model organisms including mice, interest in understanding the physiological role and molecular targets of this pathway has surged. While mTOR was already well known as a regulator of growth and protein translation, it is now clear that mTOR functions as a central coordinator of organismal metabolism in response to both environmental and hormonal signals. This review discusses recent developments in our understanding of how mTOR signaling is regulated by nutrients and the role of the mTOR signaling pathway in key metabolic tissues. Finally, we discuss the molecular basis for the negative metabolic side effects associated with rapamycin treatment, which may serve as barriers to the adoption of rapamycin or similar compounds for the treatment of diseases of aging and metabolism.

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Section: Regulation Of Mtorc1 and Mtorc2 By Nutrient And Endocrine Simentioning

confidence: 99%

Section: Regulation Of Mtorc1 and Mtorc2 By Nutrient And Endocrine Simentioning

confidence: 99%

The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging

2016

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“…Similarly, although all eumetazoans possess at least two MAF-bZIPs, the emergence of large MAF and small MAF orthology groups did not occur until after the divergence of cnidarians and bilaterians (Appendix 2.3). This study also identified a new bZIP family, called REPTOR after its Drosophila member (Tiebe et al, 2015), which emerged from an unidentified bZIP ancestor along the poriferan-eumetazoan stem. All…”

Section: The Metazoan Bzip Network Is Comprised Of Members Of Differimentioning

confidence: 99%

“…I named this family after its Drosophila orthologue, which has been recently identified as a downstream factor of the TORC1 signalling pathway (Tiebe et al, 2015). The origin of the PAR-L and OASIS-L sub-families, and REPTOR family can be traced back to being present in the last common metazoan and eumetazoan ancestor, respectively.…”

Section: Accrual Of the Animal Bzip Repertoire Over The Course Of Holmentioning

confidence: 99%

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Exploring the bZIP regulatory network in the sponge Amphimedon queenslandica: insights into the ancestral animal regulatory genome

Jindrich¹

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What genomic innovations supported the emergence of multicellular animals, over 600 million years ago, remains one of the most fundamental questions in evolutionary biology. Increasing evidence suggests that the elaboration of the regulatory mechanisms controlling gene expression, rather than gene innovation, underlies this transition. Since transcriptional regulation is largely achieved through the binding of specific transcription factors to specific cis-regulatory DNA, understanding the early evolution of these master orchestrators is key to retracing the origin of animals (metazoans). Basic leucine zipper (bZIP) transcription factors constitute one of the most ancient and conserved families of transcriptional regulators. They play a pivotal role in multiple pathways that regulate cell decisions and behaviours in all kingdoms of life. Here, I explore the early evolution and putative roles of bZIPs in a representative of one of the oldest surviving animal phyla, the marine sponge Amphimedon queenslandica.Using recently sequenced genomes from across the Eukaryota, and in particular the Metazoa, I first reconstruct the evolution of bZIPs, and document that this transcription factor superfamily has undergone multiple independent kingdom-level expansions. I present here a thorough analysis of the whole superfamily of bZIP transcription factors across the main eukaryotic clades and the putative bZIP network that was in place in the ancestor of all extant animals. To then explore the putative role of bZIP transcription factors in the metazoan ancestor, I identify the bZIP complement in the demosponge Amphimedon queenslandica (phylum Porifera). As expected for regulatory molecules, a majority of the 17 A. queenslandica bZIPs display high temporal specificity, cell-type specific localisation and are dynamically expressed throughout development. Along with bZIPs high expression across developmental stages, these characteristics point towards bZIPs having a fundamental role in this sponge. Given the consistent central role of these transcription factors in the functioning of extant animals, I infer that were already integrated in developmental and cell specific regulatory networks in the ancestral regulatory genome and supported the emergence of multicellularity.The PAR and ATF4 orthologues particularly stand out: they are highly expressed throughout Amphimedon life cycle and peak in expression at key developmental transitions. A. queenslandica PAR-bZIP AqPARa is part of the sponge circadian network. In this thesis, I establish that AqPARa is both spatially and temporally co-expressed with A. queenslandica cryptochrome AqCRY2, and that expression of both genes is entrained by light. I also explore the involvement of circadian genes that are conserved in other phyla in A. queenslandica response to light. This work provides insights III on the animal ancestral circadian regulatory network, and the evolution of PAR-bZIPs implication in the regulation of environmentally cued behaviours.A. queenslandica ATF4 ortholog...

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Parallel Evolution of Transcription Factors in Basal Metazoans

Mukherjee,

Moroz

2024

Methods in Molecular Biology

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REPTOR and REPTOR-BP Regulate Organismal Metabolism and Transcription Downstream of TORC1

Cited by 93 publications

References 54 publications

The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging

The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging

Exploring the bZIP regulatory network in the sponge Amphimedon queenslandica: insights into the ancestral animal regulatory genome

Parallel Evolution of Transcription Factors in Basal Metazoans

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