Conversion of the LIN-1 ETS Protein of Caenorhabditis elegans from a SUMOylated Transcriptional Repressor to a Phosphorylated Transcriptional Activator

摘要

The [LIN-1][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][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][1] mediates interactions with a protein predicted to be involved in transcriptional repression: the [RAD-26][2] Mi-2β/CHD4 component of the nu cleosome r emodeling and histone d eacetylation (NuRD) transcriptional repression complex. Genetic studies indicated that [rad-26][2] functions to inhibit vulval cell fates in worms. Using the yeast two-hybrid system, we showed that the [EGL-27][3]/MTA1 component of the NuRD complex binds the carboxy-terminus of [LIN-1][1] independently of [LIN-1][1] SUMOylation. [EGL-27][3] also binds [UBC-9][4], an enzyme involved in SUMOylation, and [MEP-1][5], a zinc-finger protein previously shown to bind [LIN-1][1]. Genetic studies indicate that [egl-27][3] inhibits vulval cell fates in worms. These results suggest that [LIN-1][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][1] was converted to a potent transcriptional activator in response to active ERK. We propose a model in which [LIN-1][1] recruits multiple transcriptional repressors to inhibit the 1° vulval cell fate, and phosphorylation by ERK converts [LIN-1][1] to a transcriptional activator that promotes the 1° vulval cell fate. [1]: http://www.wormbase.org/db/get?name=WBGene00002990;class=Gene [2]: http://www.wormbase.org/db/get?name=WBGene00007761;class=Gene [3]: http://www.wormbase.org/db/get?name=WBGene00001194;class=Gene [4]: http://www.wormbase.org/db/get?name=WBGene00006706;class=Gene [5]: http://www.wormbase.org/db/get?name=WBGene00003218;class=Gene