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Shared functions of plant and mammalian StAR-related lipid transfer (START) domains in modulating transcription factor activity

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Title Shared functions of plant and mammalian StAR-related lipid transfer (START) domains in modulating transcription factor activity
 
Creator Schrick, Kathrin
Bruno, Michael
Khosla, Aashima
Cox, Paige N.
Marlatt, Sara A.
Roque, Remigio A.
Nguyen, Henry C.
He, Cuiwen
Snyder, Michael P.
Singh, Daljit
Yadav, Gitanjali
 
Subject Transcription
Steroidogenic acute regulatory related lipid transfer
START
StAR
Homeodomain
HD-Zip
Glabra2
Yeast
Arabidopsis
Mouse
 
Description Accepted date: 13 August 2014
Background

Steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains were first identified from mammalian proteins that bind lipid/sterol ligands via a hydrophobic pocket. In plants, predicted START domains are predominantly found in homeodomain leucine zipper (HD-Zip) transcription factors that are master regulators of cell-type differentiation in development. Here we utilized studies of Arabidopsis in parallel with heterologous expression of START domains in yeast to investigate the hypothesis that START domains are versatile ligand-binding motifs that can modulate transcription factor activity.
Results

Our results show that deletion of the START domain from Arabidopsis Glabra2 (GL2), a representative HD-Zip transcription factor involved in differentiation of the epidermis, results in a complete loss-of-function phenotype, although the protein is correctly localized to the nucleus. Despite low sequence similarly, the mammalian START domain from StAR can functionally replace the HD-Zip-derived START domain. Embedding the START domain within a synthetic transcription factor in yeast, we found that several mammalian START domains from StAR, MLN64 and PCTP stimulated transcription factor activity, as did START domains from two Arabidopsis HD-Zip transcription factors. Mutation of ligand-binding residues within StAR START reduced this activity, consistent with the yeast assay monitoring ligand-binding. The D182L missense mutation in StAR START was shown to affect GL2 transcription factor activity in maintenance of the leaf trichome cell fate. Analysis of in vivo protein–metabolite interactions by mass spectrometry provided direct evidence for analogous lipid-binding activity in mammalian and plant START domains in the yeast system. Structural modeling predicted similar sized ligand-binding cavities of a subset of plant START domains in comparison to mammalian counterparts.
Conclusions

The START domain is required for transcription factor activity in HD-Zip proteins from plants, although it is not strictly necessary for the protein’s nuclear localization. START domains from both mammals and plants are modular in that they can bind lipid ligands to regulate transcription factor function in a yeast system. The data provide evidence for an evolutionarily conserved mechanism by which lipid metabolites can orchestrate transcription. We propose a model in which the START domain is used by both plants and mammals to regulate transcription factor activity.
We thank Shelly Diamond, Rohit Farmer, Jasreet Hundal and Ian Spalding for
technical assistance, Martin Hülskamp and Bhylahalli Srinivas for providing
SR54, Jennifer Pinkham for supplying pGEV-HIS3 and YGY13, Cathy Jackson
for providing CJY004, Johannes Hegemann for pUG35, Thierry Bergés for
pNF-1, Edgar Cahoon for EDR2 cDNA, Marcus Heisler for the REV cDNA,
James Hurley for the MLN64 cDNA, Douglas Stocco for the StAR cDNA, Arp
Schnittger for the GL2 cDNA, Taku Takahashi for ATML1 and PDF2 cDNAs,
and David Cohen for the PCTP cDNA and critical reading of the manuscript.
This work was funded by National Science Foundation grant MCB-0517758
to KS and REU Supplement grants to RAR and CH, the National Research
Initiative Competitive Grants Program grant no. 2007-35304-18453 for the
United States Department of Agriculture National Institute of Food and
Agriculture to KS, and the India Department of Biotechnology Innovative
Young Biotechnologist Award (BT/BI/12/040/2005) and BTISNET grant (BT/BI/
04/069/2006) to GY. This is contribution no. 14-409-J from the Kansas
Agricultural Experiment Station. Publication of this article was funded in part
by the Kansas State University Open Access Publishing Fund.
 
Date 2015-12-23T07:13:56Z
2015-12-23T07:13:56Z
2014
 
Type Article
 
Identifier BMC Biology, 12: 70
1741-7007
http://172.16.0.77:8080/jspui/handle/123456789/452
http://bmcbiol.biomedcentral.com/articles/10.1186/s12915-014-0070-8
10.1186/s12915-014-0070-8
 
Language en_US
 
Publisher BioMed Central Ltd