Molecular properties of the proteasome activator PA28 family proteins and gamma-interferon regulation.
BACKGROUND
Recent cDNA cloning of two homologous proteasome activators, PA28 alpha and PA28 beta, 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 gamma-interferon (gamma-IFN) was found to increase greatly the messages for PA28 alpha and PA28 beta, 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 PA28 alpha and PA28 beta. Therefore, Ki antigen was renamed PA28 gamma. Anti-PA28 gamma antibody, however, did not immunoprecipitate PA28 alpha and PA28 beta. gamma-IFN caused an almost complete loss of the PA28 gamma protein in cells without affecting its mRNA level, whereas the levels of both mRNA and protein for PA28 alpha and PA28 beta were coordinately upregulated by gamma-IFN. Finally we showed that the human chromosomal genes of PA28 alpha and PA28 gamma were located on 14q11.2 and 17q21.32-21.33, respectively.


CONCLUSIONS
PA28 gamma (equivalent to Ki antigen) is a new member of the PA28 family proteins. It exists as a unique homopolymer under non-denaturing conditions. gamma-IFN was found to induce the expression of PA28 alpha and PA28 beta, whereas it caused almost complete loss of the PA28 gamma protein in cells. The reciprocal expression of the PA28 family proteins may imply their involvement in distinct biological processes.
Tanahashi
N
N
Institute for Enzyme Research, University of Tokushima, Japan.
Yokota
K
K
Ahn
J Y
JY
Chung
C H
CH
Fujiwara
T
T
Takahashi
E
E
DeMartino
G N
GN
Slaughter
C A
CA
Toyonaga
T
T
Yamamura
K
K
Shimbara
N
N
Tanaka
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D009687:Nuclear Proteins / Q000276:immunology; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology
D001324:Autoantigens; C099558:Ki antigen; D009124:Muscle Proteins; D009687:Nuclear Proteins; C085047:PSME1 protein, human; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D046988:Proteasome Endopeptidase Complex; C486213:Psme1 protein, mouse; C486214:Psme2 protein, mouse