Y. Makino et al., TIP49, HOMOLOGOUS TO THE BACTERIAL-DNA HELICASE RUVB, ACTS AS AN AUTOANTIGEN IN HUMAN, Biochemical and biophysical research communications, 245(3), 1998, pp. 819-823
TATA-binding protein (TBP), a central component for transcriptional re
gulation, forms complexes with various transcription regulators. We ha
ve isolated a novel human cDNA for a 49-kD TBP-interacting protein (TI
P49). The human TIP49 was highly homologous to bacterial RuvB proteins
that function as a DNA helicase to promote branch migration of the Ho
lliday junction. Immunofluorescence analysis using anti-TIP49 antibody
showed a typical dot-shaped nuclear staining pattern, suggesting that
TIP49 is included in a macromolecular structure in the nucleus and ma
y participate in nuclear events such as transcription and recombinatio
n. Moreover, glycerol gradient analysis demonstrated that TIP49 is pre
sent in a macromolecular complex in nuclear extracts. Interestingly, w
e detected a high level of autoantibodies against TIP49 in sera of pat
ients with autoimmune diseases such as polymyositis/dermatomyositis an
d autoimmune hepatitis. This indicates that the autoantibody against t
his protein is a new marker for particular connective tissue diseases.
These findings provide further evidence that the macromolecular struc
tures described above are targeted by an autoimmune mechanism. The ant
i-TIP49 antibodies can be useful probes for clinical diagnosis and for
investigation of intranuclear structure. (C) 1998 Academic Press.