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Cited by 296

The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.

Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex

Open access
Sharma, Sonia, Findlay, Gregory M., Bandukwala, Hozefa S., Oberdoerffer, Shalini, Baust, Beate, Li, Zhigang, Schmidt, Valentina, Hogan, Patrick G., Sacks, David B., Rao, Anjana·2011·Proceedings of the National Academy of Sciences

Abstract

Nuclear factor of activated T cells (NFAT) proteins are Ca 2+ -regulated transcription factors that control gene expression in many cell types. NFAT proteins are heavily phosphorylated and reside in the cytoplasm of resting cells; when cells are stimulated by a rise in intracellular Ca 2+ , NFAT proteins are dephosphorylated by the Ca 2+ / calmodulin -dependent phosphatase calcineurin and translocate to the nucleus to activate target gene expression. Here we show that phosphorylated NFAT1 is present in a large cytoplasmic RNA-protein scaffold complex that contains a long intergenic noncoding RNA (lincRNA), NRON [noncoding (RNA) repressor of NFAT]; a scaffold protein, IQ motif containing GTPase activating protein (IQGAP); and three NFAT kinases, casein kinase 1, glycogen synthase kinase 3, and dual specificity tyrosine phosphorylation regulated kinase. Combined knockdown of NRON and IQGAP1 increased NFAT dephosphorylation and nuclear import exclusively after stimulation, without affecting the rate of NFAT rephosphorylation and nuclear export; and both NRON -depleted T cells and T cells from IQGAP1-deficient mice showed increased production of NFAT-dependent cytokines. Our results provide evidence that a complex of lincRNA and protein forms a scaffold for a latent transcription factor and its regulatory kinases, and support an emerging consensus that lincRNAs that bind transcriptional regulators have a similar scaffold function.

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Metadata

Authors
Sharma, S., Findlay, G. M., Bandukwala, H. S., Oberdoerffer, S., Baust, B., Li, Z., Schmidt, V., Hogan, P. G., Sacks, D. B., & Rao, A.
Venue
Proceedings of the National Academy of Sciences
Published
2011-06-27
Volume
108
Issue
28
Pages
11381-11386
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2085364628
Cited by
296
References
35
FWCI
5.53
Type
journal article
Language
en
Open access
green

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Sharma, S., Findlay, G. M., Bandukwala, H. S., Oberdoerffer, S., Baust, B., Li, Z., Schmidt, V., Hogan, P. G., Sacks, D. B., & Rao, A. (2011). Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1019711108

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