Jy. Zhang et al., A novel cytoplasmic protein with RNA-binding motifs is an autoantigen in human hepatocellular carcinoma, J EXP MED, 189(7), 1999, pp. 1101-1110
In hepatocellular carcinoma (HCC), autoantibodies to intracellular antigens
are detected in 30-40% of patients. Patients with chronic hepatitis or liv
er cirrhosis develop HCC, and when this occurs, some patients exhibit autoa
ntibodies of new specificities. It has been suggested that these novel auto
antibody responses may be immune system reactions to proteins involved ill
transformation-associated cellular events. One HCC serum shown to contain a
ntibodies to unidentified cellular antigens was used to immunoscreen a cDNA
expression library, and a full length cDNA clone was isolated with an open
reading frame encoding 556 amino acids with a predicted molecular mass of
62 kD. The 62-kD protein contained two types of RNA-binding motifs, the con
sensus sequence RNA-binding domain (CS-RBD) and four hnRNP K homology (KH)
domains. This protein, provisionally called p62, has close identity (66-70%
) to three other proteins at the amino acid sequence level, and all four pr
oteins may belong to a family having CS-RBD in the NH2-terminal region and
four KH domains in the mid-to-COOH-terminal region. The homologous proteins
are: KH domain-containing protein overexpressed in cancer (Koc); zipcode b
inding protein, a protein which binds to a conserved nucleotide element in
chicken beta-actin mRNA (ZBP1); and a protein which binds to a promoter cis
element in Xenopus laevis TFIIIA gene (B3). p62 protein is cytoplasmic in
location, and autoantibodies were found in 21% of a cohort of HCC patients.
Patients with chronic hepatitis and liver cirrhosis, conditions which are
frequent precursors to HCC, were negative for these autoantibodies, suggest
ing that the immune response might be related to cellular events leading to
transformation. However, the possible involvement of p62 autoantigen as a
factor in the transformation process remains to be elucidated.