Involvement of the NFX1-repressor complex in PKC-δ-induced repression of hTERT transcription.
The human telomerase reverse transcriptase (hTERT) gene encodes an enzyme responsible for maintaining the integrity of chromosomal ends. hTERT plays a key role in cellular immortalization, tumorigenesis and the progression of cancer. Previously, we reported that hTERT repression is required for the induction of cellular senescence. Thus, transcriptional regulation mechanisms of the hTERT gene may be related to the mechanisms of cellular senescence. In the present study, we clarified the molecular mechanism of hTERT repression by protein kinase C (PKC)-δ, one of the cellular senescence-inducing factors. The results showed that a repressor complex composed of NFX1-91, mSin3A and histone deacetylase 1 was involved in the PKC-δ-induced repression of the hTERT promoter, which resulted in the repression of hTERT transcription. These results suggest that targeted recruitment of the NFX1-91 complex to the hTERT promoter is a potential mechanism for repressing hTERT transcription and further inducing cellular senescence.
Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8581, Japan.
Shuntaro
S
Yamashita
Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8581, Japan.
Kaoru
K
Fujii
Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8581, Japan.
Chong
C
Zhao
Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8581, Japan.
Hiroshi
H
Takagi
Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8581, Japan katakura@grt.kyushu-u.ac.jp.|Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.
Yoshinori
Y
Katakura
D045744:Cell Line, Tumor; D016922:Cellular Senescence; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology*
D046912:Multiprotein Complexes; C492666:NFX1 protein, human; D012097:Repressor Proteins; C099683:SIN3A transcription factor; C497258:PRKCD protein, human; D051745:Protein Kinase C-delta; C509186:TERT protein, human; D019098:Telomerase; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D056264:Sin3 Histone Deacetylase and Corepressor Complex
NFX1-91; PKC-δ; hTERT; histone deacetylase 1(HDAC); transcription