KLF10 affects pancreatic function via the SEI-1/p21Cip1 pathway

Min-Ju Wu, Wen-Chi Wu, Hsuen-Wen Chang, Yong-Tzuo Lai, Ching-Hui Lin, Winston C Y Yu, Vincent H S Chang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

TGF-β plays a significant role in regulating pancreas islet function and maintaining their mass. KLF10, a TGF-β downstream gene, belongs to a group of Krüppel-like transcription factors that bind to the promoters of target genes and produce effects that mimic TGF-β as a tumor suppressor. Using ChIP-chip screening, SEI-1 was identified as a target gene that may be regulated by KLF10. We conducted a series of assays to verify the presence of unknown regulation events between SEI-1 and KLF10. These showed that KLF10 transcriptionally activates the SEI-1 promoter and, furthermore, induces SEI-1 protein expression in pancreatic carcinoma cells. SEI-1 is one of the key factors involved in cell cycle control through the regulation of other transcription factors such as the p21Cip1 gene. Interestingly, it has been shown previously that p21Cip1 is indirectly activated by KLF10. Our results first demonstrated that KLF10 acts as a transcriptional activator on SEI-1, which can then result in increased p21Cip1 expression. Furthermore, KLF10-deficiency in mice is associated with a decrease in the pancreatic islet mass, which is similar to the effects found in SEI-1 deficient mice. The KLF10-defect was also associated with the nuclear accumulation of the p21Cip1 in islet cells. Based on our molecular and histological findings, we conclude that KLF10 plays an important role in pancreatic β-cells and this supports a functional link between KLF10 and various cell cycle regulators, most notably in the context of the pancreas.

Original languageEnglish
Pages (from-to)53-59
Number of pages7
JournalInternational Journal of Biochemistry and Cell Biology
Volume60
DOIs
Publication statusPublished - 2015

Fingerprint

Genes
Cells
Islets of Langerhans
Pancreas
Transcription Factors
Cell Cycle Checkpoints
Tumors
Assays
Cell Cycle
Screening
Defects
Neoplasms
Proteins

Keywords

  • KLF10
  • Krüppel
  • Pancreas
  • SEI-1
  • SERTAD1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

KLF10 affects pancreatic function via the SEI-1/p21Cip1 pathway. / Wu, Min-Ju; Wu, Wen-Chi; Chang, Hsuen-Wen; Lai, Yong-Tzuo; Lin, Ching-Hui; Yu, Winston C Y; Chang, Vincent H S.

In: International Journal of Biochemistry and Cell Biology, Vol. 60, 2015, p. 53-59.

Research output: Contribution to journalArticle

Wu, Min-Ju ; Wu, Wen-Chi ; Chang, Hsuen-Wen ; Lai, Yong-Tzuo ; Lin, Ching-Hui ; Yu, Winston C Y ; Chang, Vincent H S. / KLF10 affects pancreatic function via the SEI-1/p21Cip1 pathway. In: International Journal of Biochemistry and Cell Biology. 2015 ; Vol. 60. pp. 53-59.
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AB - TGF-β plays a significant role in regulating pancreas islet function and maintaining their mass. KLF10, a TGF-β downstream gene, belongs to a group of Krüppel-like transcription factors that bind to the promoters of target genes and produce effects that mimic TGF-β as a tumor suppressor. Using ChIP-chip screening, SEI-1 was identified as a target gene that may be regulated by KLF10. We conducted a series of assays to verify the presence of unknown regulation events between SEI-1 and KLF10. These showed that KLF10 transcriptionally activates the SEI-1 promoter and, furthermore, induces SEI-1 protein expression in pancreatic carcinoma cells. SEI-1 is one of the key factors involved in cell cycle control through the regulation of other transcription factors such as the p21Cip1 gene. Interestingly, it has been shown previously that p21Cip1 is indirectly activated by KLF10. Our results first demonstrated that KLF10 acts as a transcriptional activator on SEI-1, which can then result in increased p21Cip1 expression. Furthermore, KLF10-deficiency in mice is associated with a decrease in the pancreatic islet mass, which is similar to the effects found in SEI-1 deficient mice. The KLF10-defect was also associated with the nuclear accumulation of the p21Cip1 in islet cells. Based on our molecular and histological findings, we conclude that KLF10 plays an important role in pancreatic β-cells and this supports a functional link between KLF10 and various cell cycle regulators, most notably in the context of the pancreas.

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