Editors' ChoiceCytokines

STAT92E Cuts it Short and Keeps Things Quiet

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Science's STKE  24 Sep 2002:
Vol. 2002, Issue 151, pp. tw349
DOI: 10.1126/stke.2002.151.tw349

The signal transducers and activators of transcription (STAT) transcription factors are activated by numerous extracellular signals and affect many downstream pathways critical to growth regulation and embryonic development. It is not clear how this relatively small gene family is regulated to manipulate such a complex interplay of inputs and outputs. Henrickson et al. have discovered a truncated isoform of Drosophila STAT92E that arises from an alternative promoter and may regulate STAT92E activity. Western analysis and gel-shift assays of Drosophila Schneider cell and embryo extracts probed with antibodies to different STAT92E domains revealed a truncated protein (ΔNSTAT92E) lacking the NH2 terminus. Neither the full-length nor the truncated protein were evident in larvae homozygous for the stat92E null allele, confirming that both originated from the same gene. Additional variability arises from alternative splicing, as well as alternative promoter usage. The presence of both the full-length and truncated alternate forms in larvae, embryos, and adults was confirmed by reverse transcriptase (RT)-polymerase chain reaction (PCR), and the existence of two stat92E promoters was established with 5′-rapid amplification of cDNA ends. Northern analysis and quantitative RT-PCR indicated differences in the relative expression of the different isoforms during development, suggesting a regulated alternative splicing mechanism. Conditional overexpression of ΔNSTAT92, as well as RNA interference to increase the ΔNSTAT92 to STAT92 ratio, suggest that ΔNTSTAT92 suppressed STAT92 activity in vivo. The short form of STAT92E may therefore function as an endogenous inhibitor of STAT activity that is differentially activated at different developmental stages.

M. A. Henricksen, A. Betz, M. V. Fuccillo, J. E. Darnell, Negative regulation of STAT92E by an N-terminally truncated STAT protein derived from an alternative promoter site. Genes Dev. 16, 2379-2389 (2002). [Abstract] [Full Text]

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