Coordinate stabilization of growth-regulatory transcripts in T cell malignancies

Vlasova, Irina A.; McNabb, Jennifer; Raghavan, Arvind; Reilly, Cavan; Williams, Darlisha A; Bohjanen, Kimberly; Bohjanen, Paul R.

doi:10.1016/j.ygeno.2005.04.013

Cited by 26 publications

(20 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the absence of typical ARE does not necessarily exclude the mRNA decay through 3 0 UTR. Very few among the stabilized genes in malignant T cells have the consensus AREs (Vlasova et al, 2005) although AUBP was not precisely analysed. Our reporter assay using a luciferase vector containing the 3 0 UTR of SPHK1 (Figure 4d) was consistent with the elongation of mRNA half-life and also revealed that a decrease in luciferase activity due to 3 0 UTR was much less in v-Src-NIH3T3 than in mock-NIH3T3.…”

Section: Discussionmentioning

confidence: 99%

v-Src oncogene product increases sphingosine kinase 1 expression through mRNA stabilization: alteration of AU-rich element-binding proteins

et al. 2008

View full text Add to dashboard Cite

Sphingosine kinase 1 (SPHK1) is overexpressed in solid tumors and leukemia. However, the mechanism of SPHK1 overexpression by oncogenes has not been defined. We found that v-Src-transformed NIH3T3 cells showed a high SPHK1 mRNA, SPHK1 protein and SPHK enzyme activity. siRNA of SPHK1 inhibited the growth of v-Src-NIH3T3, suggesting the involvement of SPHK1 in v-Src-induced oncogenesis. v-Src-NIH3T3 showed activations of protein kinase C-a, signal transducers and activators of transcription 3 and c-Jun NH 2 -terminal kinase. Their inhibition suppressed SPHK1 expression in v-Src-NIH3T3, whereas their overexpression increased SPHK1 mRNA in NIH3T3. Unexpectedly, the nuclear run-on assay and the promoter analysis using 5 0 -promoter region of mouse SPHK1 did not show any significant difference between mock-and v-Src-NIH3T3. Furthermore, the half-life of SPHK1 mRNA in mock-NIH3T3 was nearly 15 min, whereas that of v-Src-NIH3T3 was much longer. Examination of two AU-rich region-binding proteins, AUF1 and HuR, that regulate mRNA decay reciprocally, showed decreased total AUF1 protein associated with increased tyrosine-phosphorylated form and increased serine-phosphorylated HuR protein in v-Src-NIH3T3. Modulation of AUF1 and HuR by their overexpression or siRNA revealed that SPHK1 mRNA in v-Src-and mock-NIH3T3 was regulated reciprocally by these factors. Our results showed, for the first time, a novel mechanism of v-Src-induced SPHK1 overexpression.

show abstract

Section: Discussionmentioning

confidence: 99%

v-Src oncogene product increases sphingosine kinase 1 expression through mRNA stabilization: alteration of AU-rich element-binding proteins

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Indeed, over half of the gene expression changes in early T cell activation are a result of changes in mRNA half-life (7). The significance of mRNA decay regulation is highlighted by the fact that T cell malignancies display abnormal stabilization of numerous transcripts that encode proteins that promote cellular growth and proliferation (8).…”

mentioning

confidence: 99%

Regulation of CUG-binding Protein 1 (CUGBP1) Binding to Target Transcripts upon T Cell Activation

Beisang

Rattenbacher

Louis

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:We identified target transcripts of the RNA-binding protein CUGBP1 in resting and activated T cells. Results: T cell activation induced CUGBP1 phosphorylation, causing decreased CUGBP1 binding to target transcripts. Conclusion: CUGBP1 binding to a network of target transcripts is regulated by CUGBP1 phosphorylation following T cell activation. Significance: CUGBP1 target transcripts are coordinately regulated during T cell activation.

show abstract

“…The decay of a variety of short-lived transcripts is mediated by cis-acting sequences known as AU-rich elements (AREs) 1 that are found in the 3 0 untranslated region (UTR). The best characterized AREs are found in cytokine transcripts and other early response gene transcripts, but AREs or ARElike sequences are found in a large and diverse repertoire of cellular transcripts that are regulated in response to environmental stimuli [Bakheet et al, 2001[Bakheet et al, , 2003[Bakheet et al, , 2006Raghavan et al, 2002Raghavan et al, , 2004Vlasova et al, 2005]. Although AREs function as instability elements [Caput et al, 1986;Shaw and Kamen, 1986], they also regulate mRNA localization [Veyrune et al, 1996] and translation [Kruys et al, 1989;Han et al, 1990].…”

mentioning

confidence: 99%

Tristetraprolin recruits functional mRNA decay complexes to ARE sequences

Hau

Walsh

Ogilvie

et al. 2006

J of Cellular Biochemistry

View full text Add to dashboard Cite

AU-rich elements (AREs) in the 3' untranslated region (UTR) of numerous mammalian transcripts function as instability elements that promote rapid mRNA degradation. Tristetraprolin (TTP) is an ARE-binding protein that promotes rapid mRNA decay through mechanisms that are poorly understood. A 31 nucleotide ARE sequences from the TNF-alpha 3' UTR promoted TTP-dependent mRNA decay when it was inserted into the 3' UTR of a beta-globin reporter transcript, indicating that this short sequence was sufficient for TTP function. We used a gel shift assay to identify a TTP-containing complex in cytoplasmic extracts from TTP-transfected HeLa cells that bound specifically to short ARE sequences. This TTP-containing complex also contained the 5'-3' exonuclease Xrn1 and the exosome component PM-scl75 because it was super-shifted with anti-Xrn1 or anti-PMscl75 antibodies. RNA affinity purification verified that these proteins associated specifically with ARE sequences in a TTP-dependent manner. Using a competition binding assay, we found that the TTP-containing complex bound with high affinity to short ARE sequences from GM-CSF, IL-3, TNF-alpha, IL-2, and c-fos, but did not bind to a U-rich sequence from c-myc, a 22 nucleotide poly U sequence or a mutated GM-CSF control sequence. High affinity binding by the TTP-containing complex correlated with TTP-dependent deadenylation and decay of capped, polyadenylated transcripts in a cell-free mRNA decay assay, suggesting that the TTP-containing complex was functional. These data support a model whereby TTP functions to enhance mRNA decay by recruiting components of the cellular mRNA decay machinery to the transcript.

show abstract

Coordinate stabilization of growth-regulatory transcripts in T cell malignancies

Cited by 26 publications

References 53 publications

v-Src oncogene product increases sphingosine kinase 1 expression through mRNA stabilization: alteration of AU-rich element-binding proteins

v-Src oncogene product increases sphingosine kinase 1 expression through mRNA stabilization: alteration of AU-rich element-binding proteins

Regulation of CUG-binding Protein 1 (CUGBP1) Binding to Target Transcripts upon T Cell Activation

Tristetraprolin recruits functional mRNA decay complexes to ARE sequences

Contact Info

Product

Resources

About