Peptides derived from transcription factor EB bind to calcineurin at a similar region as the NFAT-type motif. 2017

Ruiwen Song, and Jing Li, and Jin Zhang, and Lu Wang, and Li Tong, and Ping Wang, and Huan Yang, and Qun Wei, and Huaibin Cai, and Jing Luo
Department of Biochemistry and Molecular Biology, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.

Calcineurin (CN) is involved in many physiological processes and interacts with multiple substrates. Most of the substrates contain similar motifs recognized by CN. Recent studies revealed a new CN substrate, transcription factor EB (TFEB), which is involved in autophagy. We showed that a 15-mer QSYLENPTSYHLQQS peptide from TFEB (TFEB-YLENP) bound to CN. When the TFEB-YLENP peptide was changed to YLAVP, its affinity for CN increased and it had stronger CN inhibitory activity. Molecular dynamics simulations revealed that the TFEB-YLENP peptide has the same docking sites in CN as the 15-mer DQYLAVPQHPYQWAK motif of the nuclear factor of activated T cells, cytoplasmic 1 (NFATc1-YLAVP). Moreover expression of the NFATc1-YLAVP peptide suppressed the TFEB activation in starved Hela cells. Our studies first identified a CN binding site in TFEB and compared the inhibitory capability of various peptides derived from CN substrates. The data uncovered a diversity in recognition sequences that underlies the CN signaling within the cell. Studies of CN-substrate interactions should lay the groundwork for developing selective CN peptide inhibitors that target CN-substrate interaction in vitro experiments.

UI MeSH Term Description Entries
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D050778 NFATC Transcription Factors A family of transcription factors characterized by the presence of highly conserved calcineurin- and DNA-binding domains. NFAT proteins are activated in the CYTOPLASM by the calcium-dependent phosphatase CALCINEURIN. They transduce calcium signals to the nucleus where they can interact with TRANSCRIPTION FACTOR AP-1 or NF-KAPPA B and initiate GENETIC TRANSCRIPTION of GENES involved in CELL DIFFERENTIATION and development. NFAT proteins stimulate T-CELL activation through the induction of IMMEDIATE-EARLY GENES such as INTERLEUKIN-2. NFAT Transcription Factor 1,NFAT Transcription Factor 2,NFAT Transcription Factor 3,NFAT Transcription Factor 4,NFAT Transcription Factor 5,Nuclear Factors of Activated T-Cells,NF-AT Proteins,NF-AT3 Protein,NF-AT4 Protein,NF-ATc1 Protein,NFAT Proteins,NFAT-1 Protein,NFAT-2 Protein,NFAT1 Protein,NFAT2 Protein,NFAT3 Protein,NFAT4 Protein,NFAT5 Protein,NFATC Proteins,NFATC1 Protein,NFATC1 Transcription Factor,NFATC2 Protein,NFATC2 Transcription Factor,NFATC3 Protein,NFATC3 Transcription Factor,NFATC4 Protein,NFATC4 Transcription Factor,NFATL1 Protein,NFATx Protein,NFATz Protein,Nuclear Factor of Activated T-Cells 5 Protein,Nuclear Factor of Activated T-Cells, Cytoplasmic,Nuclear Factor of Activated T-Cells, Cytoplasmic 1 Protein,Nuclear Factor of Activated T-Cells, Cytoplasmic 2 Protein,Nuclear Factor of Activated T-Cells, Cytoplasmic 3 Protein,Nuclear Factor of Activated T-Cells, Cytoplasmic 4 Protein,OREBP Protein,Osmotic Response Element Binding Protein,TonEBP Protein,Tonicity-Responsive Enhancer-Binding Protein,Transcription Factor NF-AT,Factor, NFATC1 Transcription,Factor, NFATC2 Transcription,Factor, NFATC3 Transcription,NF AT Proteins,NF AT3 Protein,NF AT4 Protein,NF ATc1 Protein,NF-AT, Transcription Factor,NFAT 1 Protein,NFAT 2 Protein,Nuclear Factor of Activated T Cells 5 Protein,Nuclear Factor of Activated T Cells, Cytoplasmic,Nuclear Factor of Activated T Cells, Cytoplasmic 1 Protein,Nuclear Factor of Activated T Cells, Cytoplasmic 2 Protein,Nuclear Factor of Activated T Cells, Cytoplasmic 3 Protein,Nuclear Factor of Activated T Cells, Cytoplasmic 4 Protein,Nuclear Factors of Activated T Cells,Tonicity Responsive Enhancer Binding Protein,Transcription Factor NF AT,Transcription Factor, NFATC1,Transcription Factor, NFATC2,Transcription Factor, NFATC3,Transcription Factor, NFATC4,Transcription Factors, NFATC
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051778 Basic Helix-Loop-Helix Leucine Zipper Transcription Factors A family of transcription factors that contain regions rich in basic residues, LEUCINE ZIPPER domains, and HELIX-LOOP-HELIX MOTIFS. BHLH-Zip Transcription Factors,BHLHLZ Transcription Factors,BHLH Zip Transcription Factors,Basic Helix Loop Helix Leucine Zipper Transcription Factors,Transcription Factors, BHLH-Zip,Transcription Factors, BHLHLZ

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