The tumor suppressor Scrib selectively interacts with specific members of the zyxin family of proteins.
The zyxin family of proteins consists of five members, ajuba, LIMD1, LPP, TRIP6 and zyxin, which localize at cell adhesion sites and shuttle to the nucleus. Previously, we established that LPP interacts with the tumor suppressor Scrib, a member of the leucine-rich repeat and PDZ (LAP) family of proteins. Here, we demonstrate that Scrib also interacts with TRIP6, but not with zyxin, ajuba, or LIMD1. We show that TRIP6 directly binds to the third PDZ domain of Scrib via its carboxy-terminus. Both proteins localize in cell-cell contacts but are not responsible to target each other to these structures. In the course of our experiments, we also characterized the nuclear export signal of human TRIP6, and show that LIMD1 is localized in focal adhesions. The binding between two of zyxin's family members and Scrib links Scrib to a communication pathway between cell-cell contacts and the nucleus, and implicates these zyxin family members in Scrib-associated functions.
Petit
Marleen M R
MM
Laboratory for Molecular Oncology, Department of Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology VIB, Herestraat 49, B-3000 Leuven, Belgium.
Crombez
Koen R M O
KR
Vervenne
Hilke B V K
HB
Weyns
Nancy
N
Van de Ven
Wim J M
WJ
D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D006023:Glycoproteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D060589:Zyxin
C485608:AJUBA protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C403807:LIMD1 protein, human; C103594:LPP protein, human; C509775:Limd1 protein, mouse; D008565:Membrane Proteins; C092282:PSMC5 protein, human; D011993:Recombinant Fusion Proteins; C480591:SCRIB protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C092842:ZYX protein, human; D060589:Zyxin; C485607:ajuba protein, mouse; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities