The protein 4.1 tumor suppressor, DAL-1, impairs cell motility, but regulates proliferation in a cell-type-specific fashion.
The neurofibromatosis 2 (NF2) tumor suppressor belongs to the Protein 4.1 family of molecules that link the actin cytoskeleton to cell surface glycoproteins. We have previously demonstrated that the NF2 protein, merlin, can suppress cell growth in vitro and in vivo as well as impair actin cytoskeleton-associated processes, such as cell spreading, attachment, and motility. Recently, we determined that expression of a second Protein 4.1 tumor suppressor, DAL-1, was lost in 60% of sporadic meningiomas, but not schwannomas. In this report, we demonstrate that DAL-1 suppresses cell proliferation in meningioma, but not schwannoma cells. Similar to merlin, DAL-1 interacts with other ERM proteins and betaII-spectrin, but not the merlin interactor protein, SCHIP-1. In addition, we report the identification of the full-length DAL-1 tumor suppressor, termed KIAA0987. Collectively, these results suggest that the two Protein 4.1 meningioma tumor suppressors, merlin and DAL-1, may be functionally distinct proteins with different mechanisms of action.
Gutmann
D H
DH
Department of Neurology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110, USA.
Hirbe
A C
AC
Huang
Z Y
ZY
Haipek
C A
CA
D008841:Actin Cytoskeleton / Q000378:metabolism; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002455:Cell Division / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary / Q000302:isolation & purification / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008579:Meningioma / Q000378:metabolism* / Q000503:physiopathology; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009442:Neurilemmoma / Q000378:metabolism* / Q000503:physiopathology; D025581:Neurofibromin 2; D009479:Neuropeptides; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C116887:EPB41L3 protein, human; C086680:ETV5 protein, human; C120904:Epb41l1 protein, rat; C513243:Etv5 protein, rat; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D025581:Neurofibromin 2; D009479:Neuropeptides; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1