1 H N, 13 C, and 15 N backbone resonance assignments of the SET/TAF-1β/I2PP2A oncoprotein (residues 23-225)

Biomol NMR Assign. 2021 Oct;15(2):383-387. doi: 10.1007/s12104-021-10034-7. Epub 2021 Jun 22.

Abstract

SET (TAF-1β/I2PP2A) is a ubiquitously expressed, multifunctional protein that plays a role in regulating diverse cellular processes, including cell cycle progression, migration, apoptosis, transcription, and DNA repair. SET expression is ubiquitous across all cell types. However, it is overexpressed or post-translationally modified in several solid tumors and blood cancers, where expression levels are correlated with worsening clinical outcomes. SET exerts its oncogenic effects primarily through the formation of antagonistic protein complexes with the tumor suppressor, protein phosphatase 2A (PP2A), and the well-known metastasis suppressor, nm23-H1. PP2A inhibition is often observed as a secondary driver of tumorigenesis and metastasis in human cancers. Preclinical studies have shown that the pharmacological reactivation of PP2A combined with potent inhibitors of the primary driver oncogene produces synergistic cell death and decreased drug resistance. Therefore, the development of novel inhibitors of the SET-PP2A interaction presents an attractive approach to reactivation of PP2A, and thereby, tumor suppression. NMR provides a unique platform to investigate protein targets in their natively folded state to identify protein and small-molecule ligands and report on the protein internal dynamics. The backbone 1HN, 13C, and 15N NMR resonance assignments were completed for the 204 amino acid nucleosome assembly protein-1 (NAP-1) domain of the human SET oncoprotein (residues 23-225). These assignments provide a vital first step toward the development of novel PP2A reactivators via SET-selective inhibition.

Keywords: I2PP2A (Inhibitor 2 of Protein Phosphatase 2A); NAP (Nucleosome Assembly Protein); Proto-oncogene; SET (Su(Var)3-9 Enhancer-of-zeste Trithorax); TAF-1β (Template-Activating Factor-Ι (β subunit).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Protein Phosphatase 2*

Substances

  • Protein Phosphatase 2