RRC ID |
45784
|
著者 |
Leight ER, Murphy JT, Fantz DA, Pepin D, Schneider DL, Ratliff TM, Mohammad DH, Herman MA, Kornfeld K.
|
タイトル |
Conversion of the LIN-1 ETS protein of Caenorhabditis elegans from a SUMOylated transcriptional repressor to a phosphorylated transcriptional activator.
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ジャーナル |
Genetics
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Abstract |
The LIN-1 ETS transcription factor plays a pivotal role in controlling cell fate decisions during development of the Caenorhabditis elegans vulva. Prior to activation of the RTK/Ras/ERK-signaling pathway, LIN-1 functions as a SUMOylated transcriptional repressor that inhibits vulval cell fate. Here we demonstrate using the yeast two-hybrid system that SUMOylation of LIN-1 mediates interactions with a protein predicted to be involved in transcriptional repression: the RAD-26 Mi-2β/CHD4 component of the nucleosome remodeling and histone deacetylation (NuRD) transcriptional repression complex. Genetic studies indicated that rad-26 functions to inhibit vulval cell fates in worms. Using the yeast two-hybrid system, we showed that the EGL-27/MTA1 component of the NuRD complex binds the carboxy-terminus of LIN-1 independently of LIN-1 SUMOylation. EGL-27 also binds UBC-9, an enzyme involved in SUMOylation, and MEP-1, a zinc-finger protein previously shown to bind LIN-1. Genetic studies indicate that egl-27 inhibits vulval cell fates in worms. These results suggest that LIN-1 recruits multiple proteins that repress transcription via both the SUMOylated amino-terminus and the unSUMOylated carboxy-terminus. Assays in cultured cells showed that the carboxy-terminus of LIN-1 was converted to a potent transcriptional activator in response to active ERK. We propose a model in which LIN-1 recruits multiple transcriptional repressors to inhibit the 1° vulval cell fate, and phosphorylation by ERK converts LIN-1 to a transcriptional activator that promotes the 1° vulval cell fate.
|
巻・号 |
199(3)
|
ページ |
761-75
|
公開日 |
2015-3-1
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DOI |
10.1534/genetics.114.172668
|
PII |
genetics.114.172668
|
PMID |
25567989
|
PMC |
PMC4349070
|
MeSH |
Animals
Caenorhabditis elegans / genetics*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Extracellular Signal-Regulated MAP Kinases / metabolism*
Female
Gene Expression Regulation*
Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism
Phosphorylation
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Sumoylation
Trans-Activators / genetics
Trans-Activators / metabolism*
Transcription Factors / genetics
Transcription Factors / metabolism*
Two-Hybrid System Techniques
Ubiquitin-Conjugating Enzymes / metabolism
Vulva / physiology
|
IF |
4.015
|
引用数 |
9
|
WOS 分野
|
GENETICS & HEREDITY
|
リソース情報 |
線虫 |
tm1611
tm1991 |