Figure 9: Model for HSF1 degradation in Huntington’s Disease. | Nature Communications

Figure 9: Model for HSF1 degradation in Huntington’s Disease.

From: Abnormal degradation of the neuronal stress-protective transcription factor HSF1 in Huntington’s disease

Figure 9

mHtt expression increases the abundance sof CK2α′ kinase and the Fbxw7 Fbox protein. CK2α′ phosphorylates HSF1 S303 and S307, inactivating HSF1 transcriptional activity and recruiting the Fbxw7 E3 ligase. The E3 ligase complex ubiquitinylates HSF1, targeting the protein for proteasomal degradation. Decreased HSF1 levels compromise the expression of HSF1 target genes that are essential for coping with misfolded and aggregated mHtt in Huntington’s Disease and for neuronal function and survival.

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