Spectrin's chimeric E2/E3 enzymatic activity.
In this minireview, we cover the discovery of the human erythrocyte α spectrin E2/E3 ubiquitin conjugating/ligating enzymatic activity and the specific cysteines involved. We then discuss the consequences when this activity is partially inhibited in sickle cell disease and the possibility that the same attenuation is occurring in multiple organ dysfunction syndrome. We finish by discussing the reasons for believing that nonerythroid α spectrin isoforms (I and II) also have this activity and the importance of testing this hypothesis. If correct, this would suggest that the nonerythroid spectrin isoforms play a major role in protein ubiquitination in all cell types. This would open new fields in experimental biology focused on uncovering the impact that this enzymatic activity has upon protein-protein interactions, protein turnover, cellular signaling, and many other functions impacted by spectrin, including DNA repair.
Department of Biochemistry and Molecular Biology, Department of Pediatrics, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Steven R
SR
Goodman
Department of Medical Physiology, College of Medicine, Texas A&M Health Science Center, College Station, TX 77843, USA.
Rachel
R
Petrofes Chapa
Department of Medical Physiology, College of Medicine, Texas A&M Health Science Center, College Station, TX 77843, USA wezimmer@medicine.tamhsc.edu.
Warren E
WE
Zimmer
D000755:Anemia, Sickle Cell / Q000201:enzymology*; D000818:Animals; D004260:DNA Repair; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D009102:Multiple Organ Failure / Q000201:enzymology*; D015398:Signal Transduction; D013049:Spectrin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
D013049:Spectrin; D044767:Ubiquitin-Protein Ligases
Spectrin; cell signaling; multiorgan organ dysfunction syndrome; proteome; red blood cell; ubiquitin