Requirement of TCF7L2 for TGF-β-dependent Transcriptional Activation of the TMEPAI Gene

Nakano, Naoko; Itoh, Shinji; Watanabe, Yuji; Maeyama, Kota; Kato, Mitsuyasu

doi:10.1074/jbc.m110.132209

Cited by 50 publications

(53 citation statements)

References 44 publications

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“…Analysis of the Id2 promoter sequence and microarray analysis revealed a binding site for transcription factor 7-like 2 (Tcf7l2) (Fig. 4I), and Tcf7l2 has been shown to be regulated by TGF-␤1 signaling (47). To examine the influence of Tgf-␤1 on Tcf7l2 expression, Tcf712 expression in Hep1-6 cells was studied using dose-response experiments with Tgf-␤1.…”

Section: Aberrant Id2 Expression Is Associated With Hepatic Dysfunctimentioning

confidence: 99%

Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction

Hamamura

Matsumoto

Ikeda

et al. 2016

Journal of Biological Chemistry

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Chronic kidney disease (CKD) is associated with an increase in serum retinol; however, the underlying mechanisms of this disorder are poorly characterized. Here, we found that the alteration of hepatic metabolism induced the accumulation of serum retinol in 5/6 nephrectomy (5/6Nx) mice. The liver is the major organ responsible for retinol metabolism; accordingly, microarray analysis revealed that the hepatic expression of most CYP genes was changed in 5/6Nx mice. In addition, D-box-binding protein (DBP), which controls the expression of several CYP genes, was significantly decreased in these mice. Cyp3a11 and Cyp26a1, encoding key proteins in retinol metabolism, showed the greatest decrease in expression in 5/6Nx mice, a process mediated by the decreased expression of DBP. Furthermore, an increase of plasma transforming growth factor-␤1 (TGF-␤1) in 5/6Nx mice led to the decreased expression of the Dbp gene. Consistent with these findings, the alterations of retinol metabolism and renal dysfunction in 5/6Nx mice were ameliorated by administration of an anti-TGF-␤1 antibody. We also show that the accumulation of serum retinol induced renal apoptosis in 5/6Nx mice fed a normal diet, whereas renal dysfunction was reduced in mice fed a retinol-free diet. These findings indicate that constitutive Dbp expression plays an important role in mediating hepatic dysfunction under CKD. Thus, the aggravation of renal dysfunction in patients with CKD might be prevented by a recovery of hepatic function, potentially through therapies targeting DBP and retinol.

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Section: Aberrant Id2 Expression Is Associated With Hepatic Dysfunctimentioning

confidence: 99%

Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction

Hamamura

Matsumoto

Ikeda

et al. 2016

Journal of Biological Chemistry

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“…The experiments were carried out according to the description above. Because TMEPAI is a direct target gene of TGF-␤ signaling (13,24), we investigated whether the C18ORF1 transcript was augmented in cells upon TGF-␤ stimulation. However, in contrast to the TMEPAI transcript, the expression of C18ORF1 mRNA was only marginally induced by TGF-␤ but not by BMP (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We speculate that C18ORF1 plays a role in fine-tuning TGF-␤ signaling under the steady state. However, TMEPAI, which is rapidly induced by TGF-␤ (13,24), can protect cells from excessive TGF-␤ signaling together with C18ORF1 to cease such extraordinary TGF-␤ signaling (Fig. 8).…”

Section: Discussionmentioning

confidence: 99%

C18 ORF1, a Novel Negative Regulator of Transforming Growth Factor-β Signaling

Nakano

Maeyama

Sakata

et al. 2014

Journal of Biological Chemistry

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Background:The structure of C18ORF1 is similar to that of TMEPAI. Results: C18ORF1 inhibits TGF-␤ signaling, but not BMP signaling, by its competition with SARA for Smad2/3 binding. Conclusion: C18ORF1 is a surveillant during the steady state of TGF-␤ signaling, although it is helped by TMEPAI to inhibit TGF-␤ signaling in a coordinated manner. Significance: C18ORF1 acts as a gatekeeper that abrogates excessive TGF-␤ signaling.

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“…Ability of TCF/LEF family members and their mutants to bind to DNA. DNAP was performed according to our previous report (10). Protein binding to DNA using rat anti-HA antibody (3F10) was detected (upper panel).…”

Section: Acknowledgementmentioning

confidence: 99%

“…TCF7L2 has already been shown to bind to Smad3 (10,13,14). Thus, we examined the interaction of Smad3 with TCF/LEF family members and their mutants.…”

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confidence: 99%

Regulation of the TMEPAI promoter by TCF7L2: the C-terminal tail of TCF7L2 is essential to activate theTMEPAIgene

2015

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We previously found that TCF7L2 could activate the TMEPAI gene efficiently, whereas LEF1 could not nearly augment its transcription. When we comprehended the functional difference(s) between TCF7L2 and LEF1 with respect to the activation of the TMEPAI gene, the C-terminal tail of TCF7L2 was needed to reveal its transcriptional activity as well as its interaction with Smad3. Consistently, both TCF7/ TCF7L2 and LEF1/TCF7L2 chimeric proteins exhibited an activity similar to TCF7L2 in transcription and Smad3 binding in contrast with LEF1 and TCF7. Our data elaborated on the diverse activity among TCF/LEF family members with respect to the transcriptional regulation of the TMEPAI gene.

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Requirement of TCF7L2 for TGF-β-dependent Transcriptional Activation of the TMEPAI Gene

Cited by 50 publications

References 44 publications

Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction

Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction

C18 ORF1, a Novel Negative Regulator of Transforming Growth Factor-β Signaling

Regulation of the TMEPAI promoter by TCF7L2: the C-terminal tail of TCF7L2 is essential to activate theTMEPAIgene

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