Transcription activating property of autoantigen SG2NA and modulating effect of WD-40 repeats

Citation
Wg. Zhu et al., Transcription activating property of autoantigen SG2NA and modulating effect of WD-40 repeats, EXP CELL RE, 269(2), 2001, pp. 312-321
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
EXPERIMENTAL CELL RESEARCH
ISSN journal
0014-4827 → ACNP
Volume
269
Issue
2
Year of publication
2001
Pages
312 - 321
Database
ISI
SICI code
0014-4827(20011001)269:2<312:TAPOAS>2.0.ZU;2-5
Abstract
Autoantibodies to intracellular proteins have been detected in sera of pati ents with various forms of cancer. Nuclear autoantigen SG2NA (S, G2 phase n uclear antigen) was isolated using autoantibodies from a patient with bladd er and lung cancers and its expression is enhanced in the S and G2 phases o f 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 inhib itory effect on transcription activation. We performed molecular swapping e xperiments by substituting the WD-40 repeats of SG2NA with those of yeast M et30 and Cdc4 and showed that the WD-40 regions from either Met30 or Cdc4 w ere capable of reproducing transcription repression function. The SG2NA WD- 40 repeats were also able to repress basal level transcription and transact ivation function of a GAL4-VP16 chimera. These observations suggest that so me 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. (C) 2001 Academic Press.