TIP49, homologous to the bacterial DNA helicase RuvB, acts as an autoantigen in human.
TATA-binding protein (TBP), a central component for transcriptional regulation, forms complexes with various transcription regulators. We have isolated a novel human cDNA for a 49-kD TBP-interacting protein (TIP49). The human TIP49 was highly homologous to bacterial RuvB proteins that function as a DNA helicase to promote branch migration of the Holliday 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 may participate in nuclear events such as transcription and recombination. Moreover, glycerol gradient analysis demonstrated that TIP49 is present in a macromolecular complex in nuclear extracts. Interestingly, we detected a high level of autoantibodies against TIP49 in sera of patients with autoimmune diseases such as polymyositis/dermatomyositis and autoimmune hepatitis. This indicates that the autoantibody against this protein is a new marker for particular connective tissue diseases. These findings provide further evidence that the macromolecular structures described above are targeted by an autoimmune mechanism. The anti-TIP49 antibodies can be useful probes for clinical diagnosis and for investigation of intranuclear structure.
Makino
Y
Y
Department of Biology, Faculty of Science, Chiba University, Japan.
Mimori
T
T
Koike
C
C
Kanemaki
M
M
Kurokawa
Y
Y
Inoue
S
S
Kishimoto
T
T
Tamura
T
T
D000074183:ATPases Associated with Diverse Cellular Activities; D001323:Autoantibodies / Q000032:analysis; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair; D018076:DNA, Complementary / Q000302:isolation & purification; D019084:Fluorescent Antibody Technique, Indirect; D006367:HeLa Cells; D006801:Humans; D008099:Liver / Q000737:chemistry; D008969:Molecular Sequence Data
D001323:Autoantibodies; D001324:Autoantigens; D001426:Bacterial Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary; C061260:RuvB protein, Bacteria; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C486549:RUVBL1 protein, human; C122079:RUVBL2 protein, human