Unusual aggregation property of recombinantly expressed cancer-testis antigens in mammalian cells

Hannaneh Ahmadi, Kohei Shogen, Kana Fujita, Tomoko Honjo, Kazuhiro Kakimi, Junichiro Futami

Research output: Contribution to journalArticlepeer-review

Abstract

Transient expression of human intracellular proteins in human embryonic kidney (HEK) 293 cells is a reliable system for obtaining soluble proteins with biologically active conformations. Contrary to conventional concepts, we found that recombinantly expressed intracellular cancer-testis antigens (CTAs) showed frequent aggregation in HEK293 cells. Although experimental subcellular localization of recombinant CTAs displayed proper cytosolic or nuclear localization, some proteins showed aggregated particles in the cell. This aggregative property was not observed in recombinant housekeeping proteins. No significant correlation was found between the aggregative and biophysical properties, such as hydrophobicity, contents of intrinsically disordered regions and expression levels, of CTAs. These results can be explained in terms of structural instability of CTAs, which are specifically expressed in the testis and aberrantly expressed in cancer cells and function as a hub in the protein-protein network using intrinsically disordered regions. Hence, we speculate that recombinantly expressed CTAs failed to form this protein complex. Thus, unfolded CTAs formed aggregated particles in the cell.

Original languageEnglish
Pages (from-to)435-443
Number of pages9
JournalJournal of biochemistry
Volume170
Issue number3
DOIs
Publication statusPublished - Sep 1 2021

Keywords

  • aggregation
  • CTAs
  • hydrophobicity
  • IDPs
  • immunotherapy

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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