Autoantibodies to intracellular proteins have been detected in sera of patients with various forms of cancer. Nuclear autoantigen SG2NA (S, G2 phase nuclear antigen) was isolated using autoantibodies from a patient with bladder and lung cancers and its expression is enhanced in the S and G2 phases of the cell cycle. Molecular cloning revealed that the C-terminal region of SG2NA contains six WD-40 repeats, motifs that are present in a large family of proteins with diverse functions. We show that the N-terminal region of SG2NA (aa 1-391) acted as a strong transcriptional activator in both yeast and mammalian cells. In contrast, the C-terminal WD-40 repeats had an inhibitory effect on transcription activation. We performed molecular swapping experiments by substituting the WD-40 repeats of SG2NA with those of yeast Met30 and Cdc4 and showed that the WD-40 regions from either Met30 or Cdc4 were capable of reproducing transcription repression function. The SG2NA WD-40 repeats were also able to repress basal level transcription and transactivation function of a GAL4-VP16 chimera. These observations suggest that some WD-40 repeats may have, as one of their functions, a negative regulatory role in the biological activities of their own and perhaps other proteins.

• PMID: 11570823
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Journal Article | Research Support, U.S. Gov't, P.H.S.

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Zhu W, Chan EK, Li J, Hemmerich P, Tan EM

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