Molecular properties of the proteasome activator PA28 family proteins and γ-interferon regulation

Nobuyuki Tanahashi, Kin Ya Yokota, Joon Young Ahn, Chin Ha Chung, Tsutomu Fujiwara, Ei Ichi Takahashi, George N. DeMartino, Clive A. Slaughter, Tetsushi Toyonaga, Ken Ichi Yamamura, Naoki Shimbara, Keiji Tanaka

Research output: Contribution to journalArticlepeer-review

116 Scopus citations


Background: Recent cDNA cloning of two homologous proteasome activators, PA28α and PA28β, indicated the presence of a structurally related third protein, Ki antigen, but a functional relationship between Ki antigen and the two PA28 proteins is unknown. Accumulating evidence has implicated an important role for PA28 in the major histocompatibility complex (MHC) class I-restricted antigen processing pathway. Recently, an immunomodulatory cytokine γ-interferon (γ-IFN) was found to increase greatly the messages for PA28α and PA28β, but not Ki antigen, in human cells. Results: Ki antigen was co-immunoprecipitated with the 20S proteasome by anti-proteasome antibody, and associated reversibly with the 20S proteasome, as observed for PA28α and PA28β. Therefore, Ki antigen was renamed PA28γ. Anti-PA28γ antibody, however, did not immunoprecipitate PA28α and PA28β. γ-IFN caused an almost complete loss of the PA28γ protein in cells without affecting its mRNA level, whereas the levels of both mRNA and protein for PA28α and PA28β were coordinately up-regulated by γ-IFN. Finally we showed that the human chromosomal genes of PA28α and PA28γ were located on 14q11.2 and 17q21.32-21.33, respectively. Conclusion: PA28γ (equivalent to Ki antigen) is a new member of the PA28 family proteins. It exists as a unique homopolymer under non-denaturing conditions. γ-IFN was found to induce the expression of PA28α and PA28β, whereas it caused almost complete loss of the PA28γ protein in cells. The reciprocal expression of the PA28 family proteins may imply their involvement in distinct biological processes.

Original languageEnglish (US)
Pages (from-to)195-211
Number of pages17
JournalGenes to Cells
Issue number3
StatePublished - 1997

ASJC Scopus subject areas

  • Genetics
  • Cell Biology


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