KF-1 ubiquitin ligase: An anxiety suppressor

Tamotsu Hashimoto-Gotoh, Naoyuki Iwabe, Atsushi Tsujimura, Keizo Takao, Tsuyoshi Miyakawa

Research output: Contribution to journalReview articlepeer-review

7 Citations (Scopus)


Anxiety is an instinct that may have developed to promote adaptive survival by evading unnecessary danger. However, excessive anxiety is disruptive and can be a basic disorder of other psychiatric diseases such as depression. The KF-1, a ubiquitin ligase located on the endoplasmic reticulum (ER), may prevent excessive anxiety; kf-1-/- mice exhibit selectively elevated anxiety-like behavior against light or heights. It is surmised that KF-1 degrades some target proteins, responsible for promoting anxiety, through the ER-associated degradation pathway, similar to Parkin in Parkinson's disease (PD). Parkin, another ER-ubiquitin ligase, prevents the degeneration of dopaminergic neurons by degrading the target proteins responsible for PD. Molecular phylogenetic studies have revealed that the prototype of kf-1 appeared in the very early phase of animal evolution but was lost, unlike parkin, in the lineage leading up to Drosophila. Therefore, kf-1-/- mice may be a powerful tool for elucidating the molecular mechanisms involved in emotional regulation, and for screening novel anxiolytic/antidepressant compounds.

Original languageEnglish
Article numberArticle 1
JournalFrontiers in Neuroscience
Issue numberMAY
Publication statusPublished - 2009

All Science Journal Classification (ASJC) codes

  • General Neuroscience


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