H₂O₂-dependent translocation of TCTP into the nucleus enables its interaction with VDR in human keratinocytes: TCTP as a further module in calcitriol signalling

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• 作者：Raphaela Rid ; Kamil Ö ; nder ; Andrea Trost ; Johann Bauer ; Helmut Hintner ; Markus Ritter ; Martin Jakab ; Ivano Costa ; Wolfgang Reischl ; Klaus Richter ; Susan MacDonald ; Marina Jendrach ; Jü ; rgen Ber
• 关键词：TCTP ; VDR ; Yeast two-hybrid ; Protein– ; protein interaction ; Skin
• 刊名：The Journal of Steroid Biochemistry and Molecular Biology
• 出版年：2010
• 出版时间：January 2010
• 年：2010
• 卷：118
• 期：1-2
• 页码：29-40
• 全文大小：1530 K

文摘

Translationally controlled tumour protein (TCTP) is an evolutionarily highly conserved molecule implicated in many processes related to cell cycle progression, proliferation and growth, to the protection against harmful conditions including apoptosis and to the human allergic response. We are showing here that after application of mild oxidative stress, human TCTP relocates from the cytoplasm to the nuclei of HaCaT keratinocytes where it directly associates with the ligand-binding domain of endogenous vitamin D₃ receptor (VDR) through its helical domain 2 (AA 71–132). Interestingly, the latter harbours a putative nuclear hormone receptor coregulatory LxxLL-like motif which seems to be involved in the interaction. Moreover, we demonstrate that VDR transcriptionally induces the expression of TCTP by binding to a previously unknown VDR response element within the TCTP promotor. Conversely, ectopically overexpressed TCTP downregulates the amount of VDR on both mRNA as well as protein level. These data, to conclude, suggest a kind of feedback regulation between TCTP and VDR to regulate a variety of (Ca²⁺ dependent) cellular effects and in this way further underscore the physiological relevance of this novel protein–protein interaction.