The Section on Neuroendocrinology has a broad interest in the role that the pineal gland plays in biology, with special interest in melatonin and how the production of melatonin is regulated by the melatonin rhythm enzyme arylalkylamine N-acetyltransferase (AANAT, EC126.96.36.199).
Current areas of research include:
- Functional analysis of the AANAT/14-3-3 regulatory complex
- Identification of new AANAT binding partners using yeast two hybrid system and affinity approaches
- Characterization of cAMP and clock dependent transcriptional mechanisms controlling AANAT gene expression
- Analysis of mechanisms involved in regulating proteasomal proteolysis of AANAT
Recent advances include:
- Discovery that a cyclic AMP operated switch controls binding of AANAT to 14-3-3 proteins
- Determination of the 3-D crystal structure of the AANAT/14-3-3 regulatory complex
- Demonstration that 14-3-3 binding activates and shields AANAT
- Use of the AANAT promoter for pineal/retina specific gene targeting
- Development of cell lines expressing AANAT
- Discovery that minute-to-minute neural control of AANAT protein in vertebrates involves blocking rapid proteasomal proteolysis
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