6sen | pdb_00006sen
TEAD4 bound to a FAM181A peptide
Structural highlights
Function[TEAD4_HUMAN] Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and non-cooperatively to the Sph and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription. Binds to the M-CAT motif.[1] [2] Publication Abstract from PubMedThe Hippo pathway is a key signaling pathway in the control of organ size and development. The most distal elements of this pathway, the TEAD transcription factors, are regulated by several proteins, such as YAP (Yes-associated protein), TAZ (transcriptional co-activator with PDZ-binding motif) and VGLL1-4 (Vestigial-like members 1-4). In this communication, combining structural data and motif searches in protein databases, we identify two new TEAD interactors: FAM181A and FAM181B. Our structural data show that they bind to TEAD via an Omega-loop as YAP/TAZ do, but only FAM181B possesses the LxxLF motif (x any amino acid) found in YAP/TAZ. The affinity of different FAM181A/B fragments for TEAD is in the low micromolar range and full-length FAM181A/B proteins interact with TEAD in cells. These findings, together with a recent report showing that FAM181A/B proteins have a role in nervous system development, suggest a potential new involvement of the TEAD transcription factors in the development of this tissue. This article is protected by copyright. All rights reserved. Identification of FAM181A and FAM181B as new interactors with the TEAD transcription factors.,Bokhovchuk F, Mesrouze Y, Delaunay C, Martin T, Villard F, Meyerhofer M, Fontana P, Zimmermann C, Erdmann D, Furet P, Scheufler C, Schmelzle T, Chene P Protein Sci. 2019 Nov 7. doi: 10.1002/pro.3775. PMID:31697419[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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