The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity
Open accessAbstract
The activity of the p53 tumor suppressor protein and the c-Jun protooncogene is regulated by posttranslational modifications, such as phosphorylation or ubiquitination. In addition, covalent attachment of the ubiquitin-like modifier SUMO appears to modulate their transcriptional activity. Sumoylation proceeds via an enzymatic pathway that is mechanistically analogous to ubiquitination, but requires a different E1-activating enzyme and Ubc9, a SUMO-specific E2-conjugating enzyme. Here, we show that two members of the PIAS family, PIAS1 and PIASxβ, act as specific E3-like ligases that promote sumoylation of p53 and c-Jun in vitro and in vivo . The PIAS proteins physically interact with both p53 and c-Jun. In addition, they bind to Ubc9, suggesting that they recruit the E2 enzyme to their respective substrate. The SUMO ligase activity requires the conserved zinc-finger domain, which is distantly related to the essential RING-finger motif, found in a subset of ubiquitin ligases. Furthermore, similar to RING-type ubiquitin ligases, PIASxβ can catalyze its own modification. Hence, these data further extend the analogy between the ubiquitin and SUMO pathway. Strikingly, PIAS proteins strongly repress the transcriptional activity of p53, suggesting that the PIAS–SUMO pathway plays a crucial role in the regulation of p53 and presumably other transcription factors.
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Specific Inhibition of Stat3 Signal Transduction by PIAS3
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Sumo, ubiquitin's mysterious cousin
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Self-citationAn E3-like Factor that Promotes SUMO Conjugation to the Yeast Septins
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SUMO-1 modification activates the transcriptional response of p53
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Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1
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Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1)
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Coping with stress: multiple ways to activate p53
Horn, H. F., & Vousden, K. H. (2007) · Oncogene · doi:10.1038/sj.onc.1210263 · Cited by 522
Myc pathways provoking cell suicide and cancer
Nilsson, J. A., & Cleveland, J. L. (2003) · Oncogene · doi:10.1038/sj.onc.1207261 · Cited by 462
Hietakangas, V., Ahlskog, J. K., Jakobsson, A. M., Hellesuo, M., Sahlberg, N. M., Holmberg, C. I., Mikhailov, A., Palvimo, J. J., Pirkkala, L., & Sistonen, L. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.8.2953-2968.2003 · Cited by 309
Regulation of MEF2 by Histone Deacetylase 4- and SIRT1 Deacetylase-Mediated Lysine Modifications
Zhao, X., Sternsdorf, T., Bolger, T. A., Evans, R. M., & Yao, T.-P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.19.8456-8464.2005 · Cited by 264
Metadata
- Authors
- Schmidt, D., & Müller, S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-02-26
- Volume
- 99
- Issue
- 5
- Pages
- 2872-2877
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2116988305
- Cited by
- 448
- References
- 29
- FWCI
- 14.36
- Type
- journal article
- Language
- en
- Open access
- bronze
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