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TGF-beta induces the expression of SAP30L, a novel nuclear protein.

Lindfors K, Viiri KM, Niittynen M, Heinonen TY, Mäki M, Kainulainen H - BMC Genomics (2003)

Bottom Line: Differential display analysis resulted in the identification of a novel TGF-beta upregulated mRNA species, the Sin3-associated protein 30-like, SAP30L.The mRNA is expressed in several human tissues and codes for a nuclear protein of 183 amino acids 70% identical with Sin3 associated protein 30 (SAP30).The predicted nuclear localization signal of SAP30L is sufficient for nuclear transport of the protein although mutating it does not completely remove SAP30L from the nuclei.

View Article: PubMed Central - HTML - PubMed

Affiliation: Paediatric Research Centre, Tampere University Hospital, Tampere, Finland. katri.lindfors@uta.fi

ABSTRACT

Background: We have previously set up an in vitro mesenchymal-epithelial cell co-culture model which mimics the intestinal crypt villus axis biology in terms of epithelial cell differentiation. In this model the fibroblast-induced epithelial cell differentiation from secretory crypt cells to absorptive enterocytes is mediated via transforming growth factor-beta (TGF-beta), the major inhibitory regulator of epithelial cell proliferation known to induce differentiation in intestinal epithelial cells. The aim of this study was to identify novel genes whose products would play a role in this TGF-beta-induced differentiation.

Results: Differential display analysis resulted in the identification of a novel TGF-beta upregulated mRNA species, the Sin3-associated protein 30-like, SAP30L. The mRNA is expressed in several human tissues and codes for a nuclear protein of 183 amino acids 70% identical with Sin3 associated protein 30 (SAP30). The predicted nuclear localization signal of SAP30L is sufficient for nuclear transport of the protein although mutating it does not completely remove SAP30L from the nuclei. In the nuclei SAP30L concentrates in small bodies which were shown by immunohistochemistry to colocalize with PML bodies only partially.

Conclusions: By reason of its nuclear localization and close homology to SAP30 we believe that SAP30L might have a role in recruiting the Sin3-histone deacetylase complex to specific corepressor complexes in response to TGF-beta, leading to the silencing of proliferation-driving genes in the differentiating intestinal epithelial cells.

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SAP30L mRNA expression in human tissues. Northern hybridization to a multi-tissue northern blot showed that a 1.3 kB transcript is expressed in all tissues examined, with higher expression in the testis and weaker in the liver and lung. A transcript of size 6.5 kB was abundantly expressed in brain and lung but not at all in liver and stomach. The lower panel shows the control hybridization with an β-actin specific probe.
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Figure 2: SAP30L mRNA expression in human tissues. Northern hybridization to a multi-tissue northern blot showed that a 1.3 kB transcript is expressed in all tissues examined, with higher expression in the testis and weaker in the liver and lung. A transcript of size 6.5 kB was abundantly expressed in brain and lung but not at all in liver and stomach. The lower panel shows the control hybridization with an β-actin specific probe.

Mentions: Sequence analysis of this transcript showed that SAP30L is identical with an mRNA transcribed from the gene FLJ11526 located in chromosome 5q33.2. The gene has four exons and the expected size of the transcribed mRNA is 1281 base pairs. Indeed, northern hybridization to a multi-tissue northern blot showed that a SAP30L-specific probe recognized an mRNA of approximately 1.3 kB (Figure 2). The mRNA was expressed in all tissues examined, with somewhat weaker expression in the liver and lung and particularly abundant expression in the testis. Interestingly, there was also a transcript of size 6.5 kB which was abundantly expressed in brain and lung but not at all in liver and stomach. As the genomic sequence did not predict an mRNA of this size, its identity remains to be established.


TGF-beta induces the expression of SAP30L, a novel nuclear protein.

Lindfors K, Viiri KM, Niittynen M, Heinonen TY, Mäki M, Kainulainen H - BMC Genomics (2003)

SAP30L mRNA expression in human tissues. Northern hybridization to a multi-tissue northern blot showed that a 1.3 kB transcript is expressed in all tissues examined, with higher expression in the testis and weaker in the liver and lung. A transcript of size 6.5 kB was abundantly expressed in brain and lung but not at all in liver and stomach. The lower panel shows the control hybridization with an β-actin specific probe.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC319701&req=5

Figure 2: SAP30L mRNA expression in human tissues. Northern hybridization to a multi-tissue northern blot showed that a 1.3 kB transcript is expressed in all tissues examined, with higher expression in the testis and weaker in the liver and lung. A transcript of size 6.5 kB was abundantly expressed in brain and lung but not at all in liver and stomach. The lower panel shows the control hybridization with an β-actin specific probe.
Mentions: Sequence analysis of this transcript showed that SAP30L is identical with an mRNA transcribed from the gene FLJ11526 located in chromosome 5q33.2. The gene has four exons and the expected size of the transcribed mRNA is 1281 base pairs. Indeed, northern hybridization to a multi-tissue northern blot showed that a SAP30L-specific probe recognized an mRNA of approximately 1.3 kB (Figure 2). The mRNA was expressed in all tissues examined, with somewhat weaker expression in the liver and lung and particularly abundant expression in the testis. Interestingly, there was also a transcript of size 6.5 kB which was abundantly expressed in brain and lung but not at all in liver and stomach. As the genomic sequence did not predict an mRNA of this size, its identity remains to be established.

Bottom Line: Differential display analysis resulted in the identification of a novel TGF-beta upregulated mRNA species, the Sin3-associated protein 30-like, SAP30L.The mRNA is expressed in several human tissues and codes for a nuclear protein of 183 amino acids 70% identical with Sin3 associated protein 30 (SAP30).The predicted nuclear localization signal of SAP30L is sufficient for nuclear transport of the protein although mutating it does not completely remove SAP30L from the nuclei.

View Article: PubMed Central - HTML - PubMed

Affiliation: Paediatric Research Centre, Tampere University Hospital, Tampere, Finland. katri.lindfors@uta.fi

ABSTRACT

Background: We have previously set up an in vitro mesenchymal-epithelial cell co-culture model which mimics the intestinal crypt villus axis biology in terms of epithelial cell differentiation. In this model the fibroblast-induced epithelial cell differentiation from secretory crypt cells to absorptive enterocytes is mediated via transforming growth factor-beta (TGF-beta), the major inhibitory regulator of epithelial cell proliferation known to induce differentiation in intestinal epithelial cells. The aim of this study was to identify novel genes whose products would play a role in this TGF-beta-induced differentiation.

Results: Differential display analysis resulted in the identification of a novel TGF-beta upregulated mRNA species, the Sin3-associated protein 30-like, SAP30L. The mRNA is expressed in several human tissues and codes for a nuclear protein of 183 amino acids 70% identical with Sin3 associated protein 30 (SAP30). The predicted nuclear localization signal of SAP30L is sufficient for nuclear transport of the protein although mutating it does not completely remove SAP30L from the nuclei. In the nuclei SAP30L concentrates in small bodies which were shown by immunohistochemistry to colocalize with PML bodies only partially.

Conclusions: By reason of its nuclear localization and close homology to SAP30 we believe that SAP30L might have a role in recruiting the Sin3-histone deacetylase complex to specific corepressor complexes in response to TGF-beta, leading to the silencing of proliferation-driving genes in the differentiating intestinal epithelial cells.

Show MeSH
Related in: MedlinePlus