Transcription factor ZBTB20: What expression is telling us of its cellular function?

ABSTRACTProteasomes are essential for protein homeostasis in eukaryotes. To preserve cellular function, transcription of proteasome subunit genes is induced in response to proteasome dysfunction caused by pathogen attacks or proteasome inhibitor drugs. In Caenorhabditis elegans, this response requires SKN-1, a transcription factor related to mammalian Nrf1/2. Here, we use comprehensive genetic analyses to identify the pathway required for C. elegans to detect proteasome dysfunction and activate SKN-1. Genes required for SKN-1 activation encode regulators of ER traffic, a peptide N-glycanase, and DDI-1, a conserved aspartic protease. DDI-1 expression is induced by proteasome dysfunction, and we show that DDI-1 is required to cleave and activate an ER-associated isoform of SKN-1. Mammalian Nrf1 is also ER-associated and subject to proteolytic cleavage, suggesting a conserved mechanism of proteasome surveillance. Targeting mammalian DDI1 protease could mitigate effects of proteasome dysfunction in aging and protein aggregation disorders, or increase effectiveness of proteasome inhibitor cancer chemotherapies.

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The genetics and the molecular functions of the PREP1 homeodomain transcription factor

The International Journal of Developmental Biology ◽

10.1387/ijdb.180238fb ◽

2018 ◽

Vol 62 (11-12) ◽

pp. 819-825 ◽

Cited By ~ 2

Author(s):

Divya Purushothaman ◽

Francesco Blasi

Keyword(s):

Dna Damage ◽

Transcription Factor ◽

Dna Replication ◽

Tumor Suppressor ◽

Embryonic Development ◽

Cellular Function ◽

Mutant Mice ◽

Homeodomain Transcription Factor ◽

Molecular Functions

Prep1 (pKnox1) is a homeodomain transcription factor of the TALE superclass whose members can act as co-factors of Hox. Prep1 is essential for embryogenesis, but in the adult it also acts as a tumor suppressor. We describe and analyze here the available mutant mice, their phenotypes and a few discordant cases. Moreover we specify the basic rules underlying the binding of Prep1 and its TALE partners to DNA, and their plasticity during embryonic development. We finally review recent data on Prep1 which indicate a very basic cellular function at the level of DNA replication and DNA damage.

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Proteasome dysfunction triggers activation of SKN-1A/Nrf1 by the aspartic protease DDI-1

eLife ◽

10.7554/elife.17721 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 96

Author(s):

Nicolas J Lehrbach ◽

Gary Ruvkun

Keyword(s):

Transcription Factor ◽

Caenorhabditis Elegans ◽

Protein Aggregation ◽

Proteasome Inhibitor ◽

Cellular Function ◽

Aspartic Protease ◽

Protein Homeostasis ◽

Genetic Analyses ◽

Proteasome Subunit ◽

C Elegans

Proteasomes are essential for protein homeostasis in eukaryotes. To preserve cellular function, transcription of proteasome subunit genes is induced in response to proteasome dysfunction caused by pathogen attacks or proteasome inhibitor drugs. In Caenorhabditis elegans, this response requires SKN-1, a transcription factor related to mammalian Nrf1/2. Here, we use comprehensive genetic analyses to identify the pathway required for C. elegans to detect proteasome dysfunction and activate SKN-1. Genes required for SKN-1 activation encode regulators of ER traffic, a peptide N-glycanase, and DDI-1, a conserved aspartic protease. DDI-1 expression is induced by proteasome dysfunction, and we show that DDI-1 is required to cleave and activate an ER-associated isoform of SKN-1. Mammalian Nrf1 is also ER-associated and subject to proteolytic cleavage, suggesting a conserved mechanism of proteasome surveillance. Targeting mammalian DDI1 protease could mitigate effects of proteasome dysfunction in aging and protein aggregation disorders, or increase effectiveness of proteasome inhibitor cancer chemotherapies.

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Author response for "Identification of Retinal Ganglion Cell Types and Brain Nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock‐in allele"

10.1002/cne.25065/v2/response1 ◽

2020 ◽

Author(s):

Nadia Parmhans ◽

Anne Drury Fuller ◽

Eileen Nguyen ◽

Katherine Chuang ◽

David Swygart ◽

...

Keyword(s):

Transcription Factor ◽

Ganglion Cell ◽

Retinal Ganglion Cell ◽

Cell Types ◽

Cre Recombinase ◽

Author Response ◽

Retinal Ganglion ◽

Brain Nuclei

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Transcription factor/DNA interactions visualized by electron spectroscopic imaging

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100122654 ◽

1992 ◽

Vol 50 (1) ◽

pp. 450-451

Author(s):

David P. Bazett-Jones ◽

Mark L. Brown

Keyword(s):

Transcription Factor ◽

Dna Sequences ◽

Transcription Initiation ◽

Molecular Mechanisms ◽

Phosphorus Content ◽

Spectroscopic Imaging ◽

Electron Spectroscopic Imaging ◽

Dna Backbone ◽

Two Parameters ◽

High Level

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.

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