The inositol phosphatase MTMR4 is a novel target of the ubiquitin ligase Nedd4.
The inositol phosphatase, MTMR4 (myotubularin-related protein 4), was identified as a novel interactor of the ubiquitin ligase Nedd4 (neural-precursor-cell-expressed developmentally down-regulated 4). hMTMR4 (human MTMR4) and Nedd4 co-immunoprecipitated and co-localized to late endosomes. The PY (Pro-Tyr) motif of hMTMR4 binds to WW (Trp-Trp) domains of hNedd4. MTMR4 expression was decreased in atrophying muscle, whereas Nedd4 expression was increased and hMTMR4 was ubiquitinated by hNedd4, suggesting that this novel interaction may underlie the biological process of muscle breakdown.
Plant
Pamela J
PJ
Department of Medicine, Clinical Sciences Division, Room 7344, Medical Science Building, University of Toronto, Toronto, 1 Kings College Circle, Ontario, Canada.
Correa
Judy
J
Goldenberg
Neil
N
Bain
James
J
Batt
Jane
J
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D056827:Endosomal Sorting Complexes Required for Transport; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D009132:Muscles / Q000378:metabolism; D000075702:Nedd4 Ubiquitin Protein Ligases; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism*; D051381:Rats; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
D056827:Endosomal Sorting Complexes Required for Transport; C000618479:NEDD4L protein, rat; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618484:Nedd4 protein, rat; D044767:Ubiquitin-Protein Ligases; C427064:MTMR4 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor