Negative regulation of Wnt signalling by HMG2L1, a novel NLK-binding protein.
BACKGROUND
Wnt signalling plays a critical role in many developmental processes and tumorigenesis. Wnt/beta-catenin signalling induces the stabilization of cytosolic beta-catenin, which interacts with TCF/LEF-1 transcription factors, thereby inducing expression of Wnt-target genes. Recent evidence suggests that a specific MAP kinase pathway involving the MAP kinase kinase kinase TAK1 and the MAP kinase NLK counteract Wnt signalling.


RESULTS
To identify NLK-interacting proteins, we performed yeast two-hybrid screening. We isolated the gene HMG2L1 and showed that injection of Xenopus HMG2L1 (xHMG2L1) mRNA into Xenopus embryos inhibited Wnt/beta-catenin-induced axis duplication and expression of Wnt/beta-catenin target genes. Moreover, xHMG2L1 inhibited beta-catenin-stimulated transcriptional activity in mammalian cells.


CONCLUSIONS
Our findings indicate that xHMG2L1 may negatively regulate Wnt/beta-catenin signalling, and that xHMG2L1 may play a role in early Xenopus development together with NLK.
Yamada
Misato
M
Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Ohkawara
Bisei
B
Ichimura
Naoya
N
Hyodo-Miura
Junko
J
Urushiyama
Seiichi
S
Shirakabe
Kyoko
K
Shibuya
Hiroshi
H
D000595:Amino Acid Sequence; D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000502:physiology*; D006801:Humans; D008845:Microinjections; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000502:physiology; D012333:RNA, Messenger / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques; D051153:Wnt Proteins; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D006609:High Mobility Group Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D020928:Mitogen-Activated Protein Kinases; C462720:nemo like kinase, Xenopus