Myopodin-mediated suppression of prostate cancer cell migration involves interaction with zyxin.
Myopodin was identified as a tumor suppressor gene that is frequently deleted in aggressive prostate cancer. Expression of myopodin protein suppresses both tumor growth and metastasis in vitro and in vivo. In the present study employing a yeast two-hybrid system, we found that zyxin, a molecule known to regulate cell motility and migration, binds with myopodin with high affinity. The binding between zyxin and myopodin seems to be direct. Screening of a series of myopodin deletion mutants and peptide competition analyses revealed that myopodin is bound by zyxin at a site located within the sequence of the 19 amino acids at the myopodin COOH terminus. Importantly, this is the same region where the tumor suppressor activity of myopodin is located. The motility and invasion suppression activity of myopodin were significantly weakened in myopodin mutants lacking this sequence. Thus, our studies suggest that zyxin may be a critical functional regulator of myopodin.
Yu
Yan Ping
YP
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. ypyu@pitt.edu
Luo
Jian-Hua
JH
D001665:Binding Sites; D002465:Cell Movement / Q000502:physiology*; D003598:Cytoskeletal Proteins; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis; D009361:Neoplasm Invasiveness; D010957:Plasmids / Q000235:genetics; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D060589:Zyxin
D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D008840:Microfilament Proteins; D011993:Recombinant Fusion Proteins; C503979:SYNPO2 protein, human; C092842:ZYX protein, human; D060589:Zyxin; D005982:Glutathione Transferase