M. Gaczynska et al., PROTEASOME SUBUNIT-X AND SUBUNIT-Y ALTER PEPTIDASE ACTIVITIES IN OPPOSITE WAYS TO THE INTERFERON-GAMMA-INDUCED SUBUNITS LMP2 AND LMP7, The Journal of biological chemistry, 271(29), 1996, pp. 17275-17280
Most antigenic peptides presented on major histocompatibility complex
class I molecules are generated by proteasomes, Interferon-gamma, whic
h stimulates antigen presentation, induces new proteasome beta-subunit
s LMP2 and LMP7, which replace the homologous beta-subunits Y (delta)
and X (epsilon). As a result, the capacity of the proteasome to cleave
model peptides increases after hydrophobic and basic residues and fal
ls after acidic residues, To clarify the function of these subunits, a
re examined the effects of overexpressing subunits X (delta) and Y (ep
silon). Transfection of the Y gene into HeLa cells stimulated the prot
easomal cleavage after acidic residues without altering other peptidas
e activities. This effect was propertional to the amount of the Y subu
nits and opposite to the effect of its homolog, LMP2. Y appears to pro
mote cleavages after acidic residues, Furthermore, in mutants lacking
the LMP genes (in contrast to wild-type cells), interferon-gamma treat
ment increased the proteasome content of Y subunits and enhanced posta
cidic cleavages. Transfection with cDNA for the X subunit reduced hydr
olysis after hydrophobic and basic residues, an effect opposite to tra
nsfection of LMP2 and LMP7, Surprisingly, transfection of X increased
the amounts not only of X, but also of Y, while decreasing LMPB conten
t. Thus, the loss of the Y subunit upon interferon-gamma treatment or
LMPB transfection accounts for the suppression of postacidic cleavages
, and the loss of X contributes to the increased hydrolysis after hydr
ophobic and basic residues. These adaptations should favor the product
ion of the kinds of peptides that are presented on major histocompatib
ility complex class I molecules.