The major-histocompatibility-complex-encoded beta-type proteasome subunits LMP2 and LMP7. Evidence that LMP2 and LMP7 are synthesized as proproteins and that cellular levels of both mRNA and LMP-containing 20S proteasomes are differentially regulated.
The proteasome (high-molecular-mass multicatalytic proteinase complex) is composed of a large number of non-identical protein subunits of the alpha and beta types. The mouse beta-type subunits LMP2 and LMP7 (LMP, low-molecular-mass protein) are encoded within the mouse major histocompatibility complex (MHC II) region, and are thought to connect the proteasome to the MHC class-I antigen-processing pathway. In the present communication, we have analysed the two proteasome subunits with regard to their identity within the proteasome complex, their protein levels, their amounts of mRNA in different mouse tissues and cell lines, and have investigated the intracellular localization of LMP2 and LMP7 subunits in thymus and liver by immunocytology. Our experiments indicate that LMP2 and LMP7 subunits are synthesized as precursor proteins of 24 kDa and 30 kDa, respectively, and that only the processed 21-kDa and 23-kDa subunits are part of the 20S proteasome complex. The proportion of LMP2-subunit-containing and LMP7-subunit-containing proteasome complexes, as well as LMP2 and LMP7 mRNA levels, vary strongly and are shown to be dependent on the tissues or cell lines analysed. Furthermore, high LMP2 and LMP7 mRNA levels do not always correlate with high protein levels, suggesting a specific translational mechanism which controls proteasome subunit synthesis. Generally, mRNA levels appear to be particularly high in those tissues which are known to be involved in MHC class-I antigen presentation. Immunocytological analysis shows a strong nuclear localization of the subunits in cells of the thymus, while in the liver they appear to be evenly distributed between the two cellular compartments. Our data support the idea that both LMP2 and LMP7 proteins are non-essential proteasome subunits which are probably involved in the regulation of proteasome activities. The function of the two subunits, however, may not be restricted to the proposed role of proteasomes in antigen presentation.
Frentzel
S
S
Zentrum für Molekulare Biologie, University of Heidelberg, Germany.
Kuhn-Hartmann
I
I
Gernold
M
M
Gött
P
P
Seelig
A
A
Kloetzel
P M
PM
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D046988:Proteasome Endopeptidase Complex; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis*; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism
D009097:Multienzyme Complexes; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex