Trends in Cell Biology
Research FocusO-GlcNAc modification: a nutritional sensor that modulates proteasome function
Section snippets
Modification of the mammalian proteasome by O-GlcNAc regulates its activity in a nutrition-dependent manner
The 26S proteasome (∼2100 kDa) is a multi-subunit complex that catalyzes ATP-dependent degradation of proteins in the cytoplasm and nucleus [22]. The proteasome consists of a 20S catalytic complex (∼670 kDa) and a 19S regulatory subcomplex (∼700 kDa). Recognition of ubiquitinated substrates for degradation by the 19S subcomplex is followed by deubiquitination and ATP-dependent unfolding of the protein. The resulting denatured polypeptide is then presented to the 20S subcomplex, where it is
Proteomic studies show that the Drosophila proteasome is modified extensively by O-GlcNAc
In a complimentary proteomic study, Sümegi et al. determined that five out of 19 proteins in the 19S regulatory subcomplex and nine out of 14 proteins in the 20S catalytic core are modified by O-GlcNAc [9]. In this study, highly purified Drosophila 19S and 20S proteasome subcomplexes were separated and analyzed using high-resolution 2D-gel electrophoresis. O-GlcNAc-modified proteins were detected (using similar methodology to Zhang et al.) and identified subsequently using mass spectrometry [9]
Concluding remarks
Two recent studies demonstrate that both the Drosophila [9] and mammalian proteasomes [10] are modified by O-GlcNAc – a post-translational modification thought to act as a nutritional sensor. A detailed proteomic study showed that at least five out of 19 proteins of the 19S proteasomal subcomplex and nine out of 14 proteins of the 20S proteasomal subcomplex of Drosophila are modified by O-GlcNAc [9]. Several proteins of the mammalian proteasome are also modified by O-GlcNAc [10]. Changes in the
Acknowledgements
We thank Chad Slawson (The Johns Hopkins University) for critical reading of the manuscript. G.W.H. acknowledges the support of NIH grants DK 61671, HD13563, CA42486.
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