Stimulation of Transcription by the Proteasome

doi:10.1126/stke.2000.38.tw5

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Sci. STKE, 27 June 2000
Vol. 2000, Issue 38, p. tw5
[DOI: 10.1126/stke.2000.38.tw5]

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STEROID RECEPTORS Stimulation of Transcription by the Proteasome

Abstract:

Certain steroid hormone receptors undergo ligand-induced degradationvia the proteasome. Lonard et al. provide intriguing evidencethat the proteasome is important both for degrading the estrogen-boundestrogen receptor ${alpha}$ (ER ${alpha}$ ) and for promoting the transcriptionalactivity of these activated receptors. Disruption of proteasomeactivity, either with inhibitors or in cells with a temperature-sensitivemutation in the ubiquitin-activating enzyme UBA, resulted instabilization of ER ${alpha}$ and inhibition of estrogen-stimulated transcriptionalactivation of reporter genes. Analysis of mutant estrogen receptorsindicated that the ability of the proteasome to regulate ER ${alpha}$ activity and to promote ER ${alpha}$ degradation was dependent on thereceptor's interaction with coactivators, but not on DNA binding. The coactivators were also targets for proteasome-mediateddegradation. Thus, the ability of the proteasome to stimulateER ${alpha}$ transcriptional activity may be by influencing the ER-coactivatorinteraction.

Lonard, D.M., Nawaz, Z., Smith, C.L., O'Malley, B.W. (2000)The 26S proteasome is required for estrogen receptor- ${alpha}$ and coactivatorturnover and for efficient estrogen receptor- ${alpha}$ transactivation.Mol. Cell 5: 939-948. [Online Journal]

Citation: Stimulation of Transcription by the Proteasome. Sci. STKE 2000, tw5 (2000).

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