Edited by Gianni CesareniKeywords: FRMD5 Adherens junction p120-Catenin E-cadherin Tumor suppressive protein a b s t r a c t FERM family proteins have been known to play an important role in tumor progression. FERMdomain containing protein 5 (FRMD5), a novel putative cytoskeletal protein, is an unknown function protein. Here, we reported that FRMD5 localized at the cell adherens junction and formed a molecular complex with p120-catenin through its C-terminal region. Functionally, we found that knockdown of endogenous FRMD5 promotes lung cancer cell migration and invasion in vitro as well as tumor growth in vivo, suggesting a tumor suppressive effect. These findings indicated that FRMD5 may play a role in p120-catenin-based cell-cell contact and is involved in the regulation of tumor progression. Structured summary of protein interactionsFRMD5 and p120 catenin colocalize by fluorescence microscopy (View interaction) FRMD5 physically interacts with p120 catenin by anti tag coimmunoprecipitation (View interaction) FRMD5 and Beta-catenin colocalize by fluorescence microscopy (View interaction) FRMD5 and gamma-catenin colocalize by fluorescence microscopy (View interaction) FRMD5 physically interacts with p120 catenin and E cadherin by anti bait coimmunoprecipitation (View interaction)

Histone modifications are deposited by chromatin modifying enzymes and read out by proteins that recognize the modified state. BRD4-NUT is an oncogenic fusion protein of the acetyl lysine reader BRD4 that binds to the acetylase p300 and enables formation of large hyperacetylated chromatin megadomains. We here examine how reading and writing contribute to larger-scale chromatin architecture. We show that NUT contains an acidic transcriptional activation domain that binds to the TAZ2 domain of p300. We use NMR to investigate the structure of the complex and found that the TAZ2 domain has an autoinhibitory role for p300. NUT-TAZ2 interaction or mutants that interfere with autoinhibition by TAZ2 allosterically activate p300. p300 activation results in a self-organizing, acetylation-dependent feed-forward reaction that enables large-scale intra- and interchromosomal interactions by bromodomain multivalent acetyl-lysine binding. We discuss how the acetylation-dependent read-write reaction drives condensation and the implications for chromatin organisation, gene regulation and dysregulation in disease.