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PIAS3 suppresses NF-κB-mediated transcription by interacting with the p65/RelA subunit
- Title
- PIAS3 suppresses NF-κB-mediated transcription by interacting with the p65/RelA subunit
- Authors
- Jang H.D.; Yoon K.; Shin Y.J.; Kim J.; Lee S.Y.
- Ewha Authors
- 이수영; 김재상
- SCOPUS Author ID
- 이수영; 김재상
- Issue Date
- 2004
- Journal Title
- Journal of Biological Chemistry
- ISSN
- 0021-9258
- Citation
- Journal of Biological Chemistry vol. 279, no. 23, pp. 24873 - 24880
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Nuclear factor-κB (NF-κB) is a transcription factor critical for key cellular processes, including immune response, apoptosis, and cell cycle progression. A yeast two-hybrid screening, using the Rel homology domain (RHD) of the p65 subunit (RelA) of NF-κB as bait, led to the isolation of PIAS3, previously identified as a specific inhibitor of STAT3. We show that PIAS3 can directly associate with p65 using an in vitro pull-down and in vivo coimmunoprecipitation assays. When overexpressed, PIAS3 inhibits NF-κB-dependent transcription induced by treatment with tumor necrosis factor α (TNF-α) or interleukin-1β or by overexpression of TNF family receptors such as RANK, TNFR1, and CD30 or signal transducers of TNF receptor-associated factors (TRAFs), including TRAF2, TRAF5, and TRAF6. Down-regulation of PIAS3 by RNA interference reverses its effect on TNF-α-mediated NF-κB activation. We found that an N-terminal region of PIAS3 is necessary for both the interaction with p65 and the transcriptional suppression activity. In addition, we found that an LXXLL coregulator signature motif located within the N-terminal region of PIAS3 is the minimal requirement for the interaction with p65. Furthermore, we demonstrate that PIAS3 interferes with p65 binding to the CBP coactivator, thereby resulting in a decreased NF-κB-dependent transcription. Taken together, these data suggest that PIAS3 may function in vivo as a modulator in suppressing the transcriptional activity of p65.
- DOI
- 10.1074/jbc.M313018200
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
- Files in This Item:
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