5uy9 | pdb_00005uy9

Prolyl isomerase Pin1 R14A mutant bound with Brd4 peptide

spinqualitylabelsall models 5uy9, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5uy9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.85Å Ligands: NIT, PE4, SO4, TPO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PIN1_HUMAN Essential PPIase that regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Displays a preference for an acidic residue N-terminal to the isomerized proline bond. Catalyzes pSer/Thr-Pro cis/trans isomerizations. Down-regulates kinase activity of BTK. Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation. Publication Abstract from PubMed BRD4 has emerged as an important factor in tumorigenesis by promoting the transcription of genes involved in cancer development. However, how BRD4 is regulated in cancer cells remains largely unknown. Here, we report that the stability and functions of BRD4 are positively regulated by prolyl isomerase PIN1 in gastric cancer cells. PIN1 directly binds to phosphorylated threonine (T) 204 of BRD4 as revealed by peptide binding and crystallographic studies and enhances BRD4's stability by inhibiting its ubiquitination. PIN1 also catalyses the isomerization of proline 205 of BRD4 and induces its conformational change, which promotes its interaction with CDK9 and increases BRD4's transcriptional activity. Substitution of BRD4 with PIN1-binding-defective BRD4-T204A mutant in gastric cancer cells reduces BRD4's stability, attenuates BRD4-mediated gene expression by impairing its interaction with CDK9 and suppresses gastric cancer cell proliferation, migration and invasion, and tumor formation. Our results identify BRD4 as a new target of PIN1 and suggest that interfering with their interaction could be a potential therapeutic approach for cancer treatment.Oncogene advance online publication, 8 May 2017; doi:10.1038/onc.2017.137. Prolyl isomerase PIN1 regulates the stability, transcriptional activity and oncogenic potential of BRD4.,Hu X, Dong SH, Chen J, Zhou XZ, Chen R, Nair S, Lu KP, Chen LF Oncogene. 2017 May 8. doi: 10.1038/onc.2017.137. PMID:28481868 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Peptidyl-prolyl cis-trans isomerase 3D structures

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