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Metaanalysis of post‐translational modifications on proteasomal proteins (555.17)
Author(s) -
Hornbeck Peter
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.555.17
Subject(s) - phosphorylation , proteasome , serine , tyrosine , microbiology and biotechnology , chemistry , ubiquitin , tyrosine phosphorylation , acetylation , biochemistry , posttranslational modification , biology , enzyme , gene
The 26S proteasome plays a critical in regulating protein degradation in multiple cellular compartments. The activity of the proteasome must respond to short term and long‐term cellular and environmental inputs efficiently. The control of phosphorylation and other post‐translational modifications (PTMs) is a central component of cellular signaling, yet little is known about the location, extent and possible roles of proteasomal PTMs. We analyzed data in PhosphoSitePlus that has been curated from >15,000 peer‐reviewed low‐throughput papers, over 100 publications of high‐throughput PTM analyses, and data from over 7,000 mass‐spec analyses performed at Cell Signaling Technology. Only experimentally verified PTMs are included in the study. They include > 150,000 phosphorylation, 50,000 ubiquitinylation, 24,000 acetylation, and ~ 8,000 methylation sites. We have analyzed the location and distribution of multiple types of PTMs on proteasome subunits and associated proteins, and have identified specific residues that are heavily modified. For example, PSMA3 is heavily phosphorylated on Ser250, but not on Tyr residues, while PSMA2 is heavily phosphorylated on four tyrosine residues including Tyr683 but not on serine residues. In contrast phosphorylation occurs infrequently on PSMA1 and PSMA4. Analysis of the topology of PTMs on available molecular structures reveal that some of the observed tyrosine and serine phosphorylation sites occur on interface residues that could potentially regulate processes such as opening the catalytic chamber and interacting with the regulatory subunits. As a contrast to the PTM landscape of the proteasome, and to place it in perspective with another cellular structure, a similar analysis of the PTM profile of nuclear pore complex will be presented. Grant Funding Source : NCI, NIGMS, NIAAA