Dickkopf homolog 1, a Wnt Signaling antagonist, is transcriptionally up-regulated via an ATF4-independent and MAPK/ERK-dependent pathway following amino acid deprivation

Publication year: 2011
Source: Biochimica et Biophysica Acta (BBA) – Gene Regulatory Mechanisms, In Press, Accepted Manuscript, Available online 13 June 2011

Dan, Zhou , Yukun, Zhang , Yuan-Xiang, Pan , Hong, Chen

Amino acid response (AAR) pathway is activated when cells are deprived of amino acids. In the present study, using the human colon cancer cell line SW480, we observed that DKK1, an antagonist of the Wnt pathway, was significantly induced at the mRNA level after the removal of amino acids from the medium. Addition of the amino alcohol histidinol, which prevents the formation of histidinyl-tRNAHis, also increased DKK1 mRNA to a level similar to that observed when cells were deprived of all amino acids. Transcriptional activity and stability of DKK1 mRNA were both increased in the amino acid-deprived condition. The induction…

 Research highlights: ► The Wnt signaling pathway was affected by amino acid deprivation through the induction of DKK1 ► Transcriptional regulation of DKK1 by amino acid deficiency was by the phosphorylation of ERK ► Knockdown of ATF4 does not inhibit the induction of DKK1 mRNA ► The study demonstrated the interactions among Wnt, AAR, and MAPK/ERK signaling pathways in a colon cancer cell line ► DKK1 is regulated by a novel amino acid response pathway that is independent of the master regulator ATF4.