Silencing Hrk

Science's STKE  08 May 2001:
Vol. 2001, Issue 81, pp. tw7
DOI: 10.1126/stke.2001.81.tw7

Sanz et al. identified a sequence in the 3′ untranslated region (UTR) of the proapoptotic hrk gene, which expresses a BH3-domain-only member of the Bcl-2 family. The 3′ UTR sequence shows similarity to a downstream regulator element (DRE) in the dynorphin gene, which acts to recruit the transcriptional repressor DREAM. DREAM bound the hrk-DRE and inhibited expression of a reporter gene in transfected cells. Investigation of two interleukin 3 (IL-3)-dependent hematopoetic cell lines confirms that DREAM is expressed and interacts with the hrk-DRE. Furthermore, DREAM was phosphorylated in response to IL-3 and its interaction with the hrk-DRE and suppression of hrk expression was enhanced by IL-3 treatment of the cells. Additionally, DREAM activity was also inhibited by increases in intracellular calcium levels (by application of a calcium ionophore) or pharmacological inhibition of phosphatidylinositol 3-kinase. However, the two cell lines did not respond to the same extent to these two treatments. Transcriptional silencing of proapoptotic genes through the regulated activation of transcriptional repressors represents one mechanism by which cytokines can promote survival of hematopoetic precursor cells.

C. Sanz, B. Mellstrom, W. A. Link, J. R. Naranjo, J. L. Fernandez-Luna, Interleukin 3-dependent activation of DREAM is involved in transcriptional silencing of the apoptotic hrk gene in hematopoietic progenitor cells. EMBO J. 20, 2286-2292. [Abstract] [Full Text]