The 4.1/ezrin/radixin/moesin domain of the DAL-1/Protein 4.1B tumour suppressor interacts with 14-3-3 proteins.

Abstract

The Protein 4.1 family contains at least two members that function as tumour suppressors, the neurofibromatosis 2 gene product merlin and the recently identified differentially expressed in adenocarcinoma of the lung (DAL-1)/Protein 4.1B molecule. DAL-1/Protein 4.1B loss is observed in a variety of tumours, including breast and lung cancers as well as meningiomas. We have previously demonstrated that DAL-1/Protein 4.1B interacts with some but not all merlin-binding proteins, raising the possibility that DAL-1/Protein 4.1B associates with additional unique proteins specific to its function as a negative growth regulator. Using yeast two-hybrid interaction cloning, we identified three 14-3-3 isoforms, beta, gamma and eta, to be DAL-1/Protein 4.1B-binding proteins. These interactions were verified by using glutathione S-transferase affinity chromatography in vitro and co-immunoprecipitation in vivo. The interaction of 14-3-3 with DAL-1/Protein 4.1B was specific, as 14-3-3 did not bind to the related Protein 4.1 family members merlin, ezrin or radixin. The DAL-1/Protein 4.1B domain that mediates 14-3-3 binding was mapped to residues Pro(244) and Leu(280) within the 4.1/ezrin/radixin/moesin domain. The identification of this novel DAL-1/Protein 4.1B-interacting protein represents the first step towards elucidating its potentially unique mechanism of action.

• Authors: Tingxi Yu, Victoria A Robb, Vinita Singh, David H Gutmann, Irene F Newsham
• Journal: The Biochemical journal (Biochem J) Vol. 365 Issue Pt 3 Pg. 783-9 (Aug 01 2002) ISSN: 0264-6021 [Print] England
• PMID: 11996670 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 14-3-3 Proteins
• Blood Proteins
• Cytoskeletal Proteins
• EPB41L3 protein, human
• Enzyme Inhibitors
• Membrane Proteins
• Microfilament Proteins
• Neurofibromin 2
• Phosphoproteins
• Protein Isoforms
• Tumor Suppressor Proteins
• ezrin
• moesin
• radixin
• Tyrosine 3-Monooxygenase

Topics

• 14-3-3 Proteins
• Blood Proteins (metabolism)
• Breast Neoplasms
• Cytoskeletal Proteins (metabolism)
• Enzyme Inhibitors (metabolism)
• Female
• Humans
• Lung Neoplasms
• Membrane Proteins (genetics, metabolism)
• Microfilament Proteins (metabolism)
• Neurofibromin 2 (metabolism)
• Phosphoproteins (metabolism)
• Protein Binding
• Protein Isoforms
• Protein Structure, Tertiary
• Tumor Cells, Cultured
• Tumor Suppressor Proteins (genetics, metabolism)
• Two-Hybrid System Techniques
• Tyrosine 3-Monooxygenase (genetics, metabolism)