A MAGEL2-deubiquitinase complex modulates the ubiquitination of circadian rhythm protein CRY1

Autor: Matthea R. Sanderson, Jocelyn M. Bischof, Mercedes Zoeteman, Abigail Seewald, K. Vanessa Carias, Rachel Wevrick
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Excessive daytime sleepiness
Biochemistry
Deubiquitinating enzyme
Ubiquitin-Specific Peptidase 7
Mice
0302 clinical medicine
Ubiquitin
Medicine and Health Sciences
Post-Translational Modification
0303 health sciences
Multidisciplinary
Deubiquitinating Enzymes
Brain
Phenotype
Cell biology
Circadian Rhythm
Circadian Rhythms
Neurology
Medicine
Suprachiasmatic Nucleus
medicine.symptom
Anatomy
Prader-Willi syndrome
Cryptochrome-1
Research Article
Protein family
Science
Immunoblotting
Hypothalamus
Molecular Probe Techniques
Biology
Research and Analysis Methods
Transfection
03 medical and health sciences
Antigens
Neoplasm
medicine
Animals
Circadian rhythm
Clinical genetics
Molecular Biology Techniques
Gene
Molecular Biology
030304 developmental biology
Ubiquitination
Biology and Life Sciences
Proteins
Cryptochromes
Disorders of imprinting
biology.protein
Sleep Disorders
Chronobiology
030217 neurology & neurosurgery
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 4, p e0230874 (2020)
ISSN: 1932-6203
Popis: MAGEL2 encodes the L2 member of the MAGE (melanoma antigen) protein family. Protein truncating mutations in MAGEL2 cause Schaaf-Yang syndrome, and MAGEL2 is one of a small set of genes deleted in Prader-Willi syndrome. Excessive daytime sleepiness, night-time or early morning waking, and narcoleptic symptoms are seen in people with Prader-Willi syndrome and Schaaf-Yang syndrome, while mice carrying a gene-targeted Magel2 deletion have disrupted circadian rhythms. These phenotypes suggest that MAGEL2 is important for the robustness of the circadian rhythm. However, a cellular role for MAGEL2 has yet to be elucidated. MAGEL2 influences the ubiquitination of substrate proteins to target them for further modification or to alter their stability through proteasomal degradation pathways. Here, we characterized relationships among MAGEL2 and proteins that regulate circadian rhythm. The effect of MAGEL2 on the key circadian rhythm protein cryptochrome 1 (CRY1) was assessed using in vivo proximity labelling (BioID), immunofluorescence microscopy and ubiquitination assays. We demonstrate that MAGEL2 modulates the ubiquitination of CRY1. Further studies will clarify the cellular role MAGEL2 normally plays in circadian rhythm, in part through ubiquitination and regulation of stability of the CRY1 protein.
Databáze: OpenAIRE
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