title: CREPT/RPRD1B, a recently identified novel protein highly expressed in tumors, enhances the β-catenin·TCF4 transcriptional activity in response to Wnt signaling.
abstract: CREPT (cell cycle-related and expression elevated protein in tumor)/RPRD1B (regulation of nuclear pre-mRNA domain-containing protein 1B), highly expressed during tumorigenesis, was shown to enhance transcription of CCND1 and to promote cell proliferation by interacting with RNA polymerase II. However, which signaling pathway is involved in CREPT-mediated activation of gene transcription remains unclear. In this study, we reveal that CREPT participates in transcription of the Wnt/β-catenin signaling activated genes through the β-catenin and the TCF4 complex. Our results demonstrate that CREPT interacts with both β-catenin and TCF4, and enhances the association of β-catenin with TCF4, in response to Wnt stimulation. Furthermore, CREPT was shown to occupy at TCF4 binding sites (TBS) of the promoters of Wnt-targeted genes under Wnt stimulation. Interestingly, depletion of CREPT resulted in decreased occupancy of β-catenin on TBS, and over-expression of CREPT enhances the activity of the β-catenin·TCF4 complex to initiate transcription of Wnt target genes, which results in up-regulated cell proliferation and invasion. Our study suggests that CREPT acts as an activator to promote transcriptional activity of the β-catenin·TCF4 complex in response to Wnt signaling.
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, National Engineering Laboratory for Anti-tumor Therapeutics, Tsinghua University, Beijing 100084,; State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, and.
authors: Yanquan
authors: Y
authors: Zhang
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, National Engineering Laboratory for Anti-tumor Therapeutics, Tsinghua University, Beijing 100084,; State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, and.
authors: Chunxiao
authors: C
authors: Liu
authors: The Second People's Hospital of Zhuhai, Guangdong 519000, China.
authors: Xiaolin
authors: X
authors: Duan
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, National Engineering Laboratory for Anti-tumor Therapeutics, Tsinghua University, Beijing 100084,; State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, and.
authors: Fangli
authors: F
authors: Ren
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, National Engineering Laboratory for Anti-tumor Therapeutics, Tsinghua University, Beijing 100084.
authors: Shan
authors: S
authors: Li
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, National Engineering Laboratory for Anti-tumor Therapeutics, Tsinghua University, Beijing 100084,; State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, and.
authors: Zhe
authors: Z
authors: Jin
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, National Engineering Laboratory for Anti-tumor Therapeutics, Tsinghua University, Beijing 100084,; State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, and.
authors: Yinyin
authors: Y
authors: Wang
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, National Engineering Laboratory for Anti-tumor Therapeutics, Tsinghua University, Beijing 100084,; State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, and.
authors: Yarui
authors: Y
authors: Feng
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, National Engineering Laboratory for Anti-tumor Therapeutics, Tsinghua University, Beijing 100084.
authors: Zewen
authors: Z
authors: Liu
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, National Engineering Laboratory for Anti-tumor Therapeutics, Tsinghua University, Beijing 100084,; State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, and.
authors: Zhijie
authors: Z
authors: Chang
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C571224:CREPT protein, mouse; D018797:Cell Cycle Proteins; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; C571225:RPRD1B protein, human; C532096:TCF4 protein, human; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin
keywords: CREPT; Cyclin D1; RPRD1B; T-cell Factor (TCF); Transcription Coactivator; Wnt Pathway; β-Catenin (B-catenin)