Ubiquitin cross-reactive protein (UCRP) is an interferon-inducible ubi
quitin homologue which is constitutively present in cells and can be c
onjugated to other proteins. Using a characterized polyclonal antiseru
m to UCRP, immnunohistochemical localization of UCRP was performed on
paraffin-processed normal human tissues and in human tissues known to
contain ubiquitinated intracellular inclusions. The antibody to UCRP i
mmunostained lymphoid cells, striated and smooth muscle, several epith
elia, and neurons. The level of staining varied greatly between tissue
s but was in a consistent punctate pattern. Localization to neuromuscu
lar junctions and striations is similar to that described for antisera
to ubiquitin-protein conjugates. Inclusion bodies characterized by im
munoreactivity to anti-ubiquitin were not detected by the antibody to
UCRP. Importantly, because UCRP may also be detected by antisera to co
njugated ubiquitin, future studies on the distribution of ubiquitin in
tissue sections must now take account of possible cross-reactivity wi
th UCRP.