IRES‐dependent translational control of <i>Cbfa1/Runx2</i> expression

Xiao, Zhousheng; Simpson, Lin; Quarles, L. Darryl

doi:10.1002/jcb.10375

Cited by 40 publications

(44 citation statements)

References 49 publications

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“…The mouse lck proximal promoter was required for tissue-specific expression in the thymus and mtβ was a critical transactivator for the proximal promoter (Reynolds et al, 1990;Yamada et al, 2001). The phenomenon of a differential expression pattern from a single gene by alternative promoters is very common, and is often related to tissuespecific expression of that gene (Christophi et al, 2004;Hai et al, 2001;Jian et al, 2006;Tao et al, 2001;Xiao et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Mouse 4-1BB Expression: Multiple Promoter Usages and a Splice Variant

Kim

Kwon

2011

Molecules and Cells

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The expression of 4-1BB has been known to be dependent on T cell activation. Recent studies have, however, revealed that 4-1BB expression is not restricted to T cells. We sought to determine the molecular basis for the differential gene expression. Here we report the expression pattern of two mouse 4-1BB transcripts, type I and type II. Whereas the type I transcript was specifically expressed on immune organ as previously reported, the type II transcript was ubiquitously expressed in tissues and various cell lines. However, both type I and type II transcript were highly induced on activated T cells. Primer extension assay of the two 4-1BB transcripts suggested that mouse 4-1BB had more than two transcripts. Using luciferase assay we have identified three promoter regions (PI, PII and PIII), which located on upstream region of second exon 1, first exon 1, and exon 2, respectively. In particular, the type I transcript was preferentially induced when naïve T cells are stimulated by anti-CD3 monoclonal antibody (mAb) since NF-κB specifically binds to the putative NF-κB element of PI. We have also shown that a splice variant, in which the transmembrane domain was deleted, could inhibit 4-1BB signaling. The splicing variant was highly induced by TCR stimulation. Our results reveal 4-1BB also has a negative regulation system through soluble 4-1BB produced from a splice variant induced under activation conditions.

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Section: Discussionmentioning

confidence: 99%

Regulation of Mouse 4-1BB Expression: Multiple Promoter Usages and a Splice Variant

Kim

Kwon

2011

Molecules and Cells

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“…However, it has been shown that Runx2 expression can be modulated in several ways, including direct stimulation of gene expression, post-translational modification, and proteinprotein interactions (Li et al, 2004b;Bae and Lee, 2006;Shen et al, 2006). It is known that Runx2 mRNA can be translated by capdependent and cap independent internal ribosomal entry site (IRES) mechanisms (Xiao et al, 2003;Elango et al, 2006;Nishio et al, 2006). IRES-dependent translation adds an additional level at which expression of this gene is regulated.…”

Section: Discussionmentioning

confidence: 99%

Regulation and functional role of the Runt-related transcription factor-2 in pancreatic cancer

et al. 2007

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Recent evidence suggests that Runt-related transcription factors play a role in different human tumours. In the present study, the localisation of the Runt-related transcription factor-2 (Runx2), its transcriptional activity, as well as its regulation of expression was analysed in human pancreatic ductal adenocarcinoma (PDAC). Quantitative real-time PCR and immunohistochemistry were used for Runx2 expression and localisation analysis. Runt-related transcription factor-2 expression was silenced using specific siRNA oligonucleotides in pancreatic cancer cells (Panc-1) and immortalised pancreatic stellate cells (IPSCs). Overexpression of Runx2 was achieved using a full-length expression vector. TGF-b1, BMP2, and other cytokines were assessed for their potential to regulate Runx2 expression. There was a 6.1-fold increase in median Runx2 mRNA levels in PDAC tissues compared to normal pancreatic tissues (Po0.0001). Runt-related transcription factor-2 was localised in pancreatic cancer cells, tubular complexes, and PanIN lesions of PDAC tissues as well as in tumour-associated fibroblasts/stellate cells. Coculture of IPSCs and Panc-1 cells, as well as treatment with TGF-b1 and BMP2, led to increased Runx2 expression in Panc-1 cells. Runt-related transcription factor-2 overexpression was associated with decreased MMP1 release as well as decreased growth and invasion of Panc-1 cells. These effects were reversed by Runx2 silencing. In conclusion, Runx2 is overexpressed in PDAC, where it is regulated by certain cytokines such as TGF-b1 and BMP2 in an auto-and paracrine manner. In addition, Runx2 has the potential to regulate the transcription of extracellular matrix modulators such as SPARC and MMP1, thereby influencing the tumour microenvironment.

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“…DNase I-treated total RNA (1.0 g) was reverse-transcribed into cDNA with the reverse primer described before (44). The reverse transcription reaction was incubated at 50°C for 30 min.…”

Section: Measurement Of Alkaline Phosphatase Activity and Mineralizatmentioning

confidence: 99%

“…Equal quantities of protein were subjected to NuPAGE TM 4 -12% Bis-Tris gel (Invitrogen) and were analyzed with standard Western blot protocols (horseradish peroxidase-conjugated secondary antibodies from Santa Cruz Biotechnology and ECL from Amersham Biosciences). RUNX2 (sc-10758) and lamin A/C (sc-6215) antibodies from Santa Cruz Biotechnology were used according to the manufacturer's instructions (44).…”

Section: Real-time Rt-pcr and Westernmentioning

confidence: 99%

Cilia-like Structures and Polycystin-1 in Osteoblasts/Osteocytes and Associated Abnormalities in Skeletogenesis and Runx2 Expression

Xiao

Zhang

Mahlios

et al. 2006

Journal of Biological Chemistry

232

260

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We examined the osteoblast/osteocyte expression and function of polycystin-1 (PC1), a transmembrane protein that is a component of the polycystin-2 (PC2)-ciliary mechano-sensor complex in renal epithelial cells. We found that MC3T3-E1 osteoblasts and MLO-Y4 osteocytes express transcripts for PC1, PC2, and the ciliary proteins Tg737 and Kif3a. Immunohistochemical analysis detected cilia-like structures in MC3T3-E1 osteoblastic and MLO-Y4 osteocyte-like cell lines as well as primary osteocytes and osteoblasts from calvaria. Pkd1 m1Bei mice have inactivating missense mutations of Pkd1 gene that encode PC1. Pkd1 m1Bei homozygous mutant mice demonstrated delayed endochondral and intramembranous bone formation, whereas heterozygous Pkd1 m1Bei mutant mice had osteopenia caused by reduced osteoblastic function. Heterozygous and homozygous Pkd1 m1Bei mutant mice displayed a gene dose-dependent decrease in the expression of Runx2 and osteoblastrelated genes. In addition, overexpression of constitutively active PC1 C-terminal constructs in MC3T3-E1 osteoblasts resulted in an increase in Runx2 P1 promoter activity and endogenous Runx2 expression as well as an increase in osteoblast differentiation markers. Conversely, osteoblasts derived from Pkd1 m1Bei homozygous mutant mice had significant reductions in endogenous Runx2 expression, osteoblastic markers, and differentiation capacity ex vivo. Co-expression of constitutively active PC1 C-terminal construct into Pkd1 m1Bei homozygous osteoblasts was sufficient to normalize Runx2 P1 promoter activity. These findings are consistent with a possible functional role of cilia and PC1 in anabolic signaling in osteoblasts/osteocytes.

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IRES‐dependent translational control of Cbfa1/Runx2 expression

Cited by 40 publications

References 49 publications

Regulation of Mouse 4-1BB Expression: Multiple Promoter Usages and a Splice Variant

Regulation of Mouse 4-1BB Expression: Multiple Promoter Usages and a Splice Variant

Regulation and functional role of the Runt-related transcription factor-2 in pancreatic cancer

Cilia-like Structures and Polycystin-1 in Osteoblasts/Osteocytes and Associated Abnormalities in Skeletogenesis and Runx2 Expression

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