Department of Genetics

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Ke Li paper published

Li, K. and Baker, N.E. (2018) Regulation of the Drosophila Id protein Extra macrochaetae by proneural dimerization partners. Elife 7:333967 PMID 29687780

Formation of almost all neurons requires a small class of proneural transcription factors that are found in the genomes all multicellular animals. These proteins dimerize with "HLH" proteins that are present in every cell to trigger the onset of neural gene expression. Although the detailed mechanisms are not understood, these HLH partner proteins are implicated in many human diseases, including schizophrenia, atherosclerosis, and others. Our study identifies a major way in which these partner proteins are regulated

Our research leads to two novel findings. First, it was previously thought that the expression levels of these HLH proteins was determined by the level of transcription of their genes. Our study shows that in fact differences in protein stability are more important. Secondly, it was previously thought that the competence of cells to respond to proneural transcription factors was determined by the pre-existing levels of partner proteins that were available. Now we find that in fact it is the reverse, the levels of these proteins are altered by the proneural proteins, through changes in protein stability.

This basic research was conducted using the fruitfly Drosophila melanogaster, which conveniently has many fewer HLH proteins than humans do. The research suggests that in the future, attempts to develop therapies for diseases that are affected by HLH genes, including schizophrenia and lymphomas among others, could focus on factors that affect the stability of these proteins.

Dr. Ke Li was a PhD student in Dr. Baker’s lab and is now a postdoc at the University of California, San Francisco.

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