Phopsho Ubiquitin: [Ser(PO3H2)65]-Ubiquitin 2016/04/13

In 2014, Koyano et al.1) and other groups2)-4) reported a novel function of ubiquitin, that [Ser(PO3H2)65]-ubiquitin (phosphorylated ubiquitin at Ser65) is clarified to be an essential player in mitochondrial quality control. PINK1 (PTEN-induced protein kinase 1) phosphorylates ubiquitin at Ser65, as well as Parkin (E3 ubiquitin ligase) at the similar Ser residue in its ubiquitin-like domain upon depolarization of mitochondrial membrane (mitochondria damage), which follows the activation of latent Parkin E3 by retrieving the catalytic cysteine from autoinhibition.

phosphoUb_en

After this initial observation, research in relation to phosphorylation of ubiquitin has been increasing tremendously, including: i) activation mechanism of Parkin by [Ser(PO3H2)65]-ubiquitin by crystallographic analysis using Pediculus humanus Parkin5), ii) disposal of damaged mitochondria through mitophagic pathway where [Ser(PO3H2)65]-ubiquitin, phosphorylated by PINK1, is involved in inducing autophagy receptor recruitment6)

These experimental results imply that [Ser(PO3H2)65]-ubiquitin may shed light on the research of Parkinson’s disease which is associated with mitochondrial dysfunction.

　

Code Compound Quantity
4486-v [Ser(PO3H2)65]-Ubiquitin 50 μg vial
3207-v Ubiquitin Aldehyde 50 μg vial

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  1. Nature, 510, 162 (2014). DOI: 10.1038/nature13392 (Original)
  2. J. Cell Biol., 205, 143 (2014). DOI: 10.1083/jcb.201402104 (Original)
  3. Biochem. J., 460, 127 (2014). DOI: 10.1042/BJ20140334 (Original)
  4. Mol. Cell, 56, 360 (2014). DOI: 10.1016/j.molcel.2014.09.007 (Original)
  5. Nature, 524, 370 (2015). DOI: 10.1038/nature14879 (Role in Parkin Activation)
  6. Nature, 524, 309 (2015). DOI: 10.1038/nature14893 (Role in Mitophagy)

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