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Comments on Blackwell TK et al. (2000) East Coast Worm Meeting "A conserved transcription motif suggesting functional parallels betweenC. elegans SKN-1 and Cap 'n' Collar-related bZIP proteins" (0)
Overview
Blackwell TK, Walker AK, An JH, Shi Y, & See R (2000). A conserved transcription motif suggesting functional parallels betweenC. elegans SKN-1 and Cap 'n' Collar-related bZIP proteins presented in East Coast Worm Meeting. Unpublished information; cite only with author permission.
In C. elegans embryogenesis, the maternal factor SKN-1 plays a pivital role in the specification of gut, some body wall muscle and pharynx. The acitivity of SKN-1 also requires mutliple inputs from transcriptional co-factor interactions as well as defined signal transduction pathways. To understand how SKN-1 responds to different blastomere enviroments and coordinates distinct developmental outcomes, we have begun to analyze SKN-1 structure and function. The SKN-1 DNA binding region is related to those of the Cap n Collar (CNC) family of basic leucine zipper (bZIP) proteins, which bind DNA as dimers, but SKN-1 is unique in that it binds DNA as a monomer. The similarity between SKN-1 and CNC proteins, such as NF-E2, NRF-1 and NRF-2, might simply reflect overlapping DNA binding strategies, but bZIP containing CNC proteins are not present in C. elegans, and no momermeric SKN-1 like protein has been identifed outside of nematodes. However, the involvement of CNC proteins, such as NRF-1, in endoderm and mesoderm development suggests that they may be close functional counterparts to SKN-1. With a cell culture assay, we have determined that SKN-1 induces transcription through three potent activation domains. The functional core of one of these domains is a short sequence motif, the DIDLID element, which is highly conserved in NRF-1 and NRF-2. The DIDLID element is important for SKN-1-driven transcription, suggesting that it is also likely to be significant in NRF proteins. In addition, SKN-1 binds to and activates transcription through the p300/CBP coactivator, supporting the genetic prediction that SKN-1 recruits the C. elegans p300/CBP ortholog, CBP-1. The role of CBP-1 in SKN-1 target gene activation is currently under investigation. The DIDLID element appears to act independently of p300/CBP, however, suggesting that it has a distinct conserved target. Thus, the evolutionary preservation of the DIDLID transcriptional element suggests that SKN-1 and NRF proteins interact with analogous co-factors, and may have preserved functional similarities despite diverging in their DNA binding domains.