ERK-mediated NELF-A phosphorylation promotes transcription elongation of immediate-early genes by releasing promoter-proximal pausing of RNA polymerase II.

Growth factor-induced, ERK-mediated induction of immediate-early genes (IEGs) is crucial for cell growth and tumorigenesis. Although IEG expression is mainly regulated at the level of transcription elongation by RNA polymerase-II (Pol-II) promoter-proximal pausing and its release, the role of ERK in this process remains unknown. Here, we identified negative elongation factor (NELF)-A as an ERK substrate. Upon growth factor stimulation, ERK phosphorylates NELF-A, which dissociates NELF from paused Pol-II at the promoter-proximal regions of IEGs, allowing Pol-II to resume elongation and produce full-length transcripts. Furthermore, we found that in cancer cells, PP2A efficiently dephosphorylates NELF-A, thereby preventing aberrant IEG expression induced by ERK-activating oncogenes. However, when PP2A inhibitor proteins are overexpressed, as is frequently observed in cancers, decreased PP2A activity combined with oncogene-mediated ERK activation conspire to induce NELF-A phosphorylation and IEG upregulation, resulting in tumor progression. Our data delineate previously unexplored roles of ERK and PP2A inhibitor proteins in carcinogenesis.

Role of transcription factor NimR (YeaM) in sensitivity control of Escherichia coli to 2-nitroimidazole.

The binding site(s) on the Escherichia coli genome was determined for an uncharacterized AraC/XylS superfamily transcription factor YeaM by using the in vitro genomic SELEX screening system. The only one clear binding target of YeaM was found to locate in the spacer between the divergently transcribed yeaM and yeaN genes. After the phenotype microarray analysis, the major facilitator superfamily transporter YeaN was found to confer E. coli the resistance to 2-nitroimidazole, the antibacterial and antifungal antibiotic, suggesting that YeaN plays a role in 2-nitromidazole efflux. Purified YeaM bound to three sites within this yeaM-yeaN spacer region. Several lines of in vitro and in vivo evidence indicate that YeaM regulates transcription of both the yeaM gene itself and the yeaNO operon. Taken together we propose to rename yeaN to nimT (nitroimidazole transporter) and yeaM to nimR (regulator of nimT).