The high mobility group protein HMG20A cooperates with the histone reader PHF14 to modulate TGF beta and Hippo pathways
Por:
Gomez-Marin, E, Posavec-Marjanovic, M, Zarzuela, L, Basurto-Cayuela, L, Guerrero-Martinez, JA, Arribas, G, Yerbes, R, Ceballos-Chavez, M, Rodriguez-Paredes, M, Tome, M, Duran, RV, Buschbeck, M and Reyes, JC
Publicada:
23 sep 2022
Ahead of Print:
1 sep 2022
Resumen:
High mobility group (HMG) proteins are chromatin regulators with essential functions in development, cell differentiation and cell proliferation. The protein HMG20A is predicted by the AlphaFold2 software to contain three distinct structural elements, which we have functionally characterized: i) an amino-terminal, intrinsically disordered domain with transactivation activity; ii) an HMG box with higher binding affinity for double-stranded, four-way-junction DNA than for linear DNA; and iii) a long coiled-coil domain. Our proteomic study followed by a deletion analysis and structural modeling demonstrates that HMG20A forms a complex with the histone reader PHF14, via the establishment of a two-stranded alpha-helical coiled-coil structure. siRNA-mediated knockdown of either PHF14 or HMG20A in MDA-MB-231 cells causes similar defects in cell migration, invasion and homotypic cell-cell adhesion ability, but neither affects proliferation. Transcriptomic analyses demonstrate that PHF14 and HMG20A share a large subset of targets. We show that the PHF14-HMG20A complex modulates the Hippo pathway through a direct interaction with the TEAD1 transcription factor. PHF14 or HMG20A deficiency increases epithelial markers, including E-cadherin and the epithelial master regulator TP63 and impaired normal TGF beta-trigged epithelial-to-mesenchymal transition. Taken together, these data indicate that PHF14 and HMG20A cooperate in regulating several pathways involved in epithelial-mesenchymal plasticity.
Filiaciones:
Gomez-Marin, E:
Univ Pablo Olavide CSIC USE UPO, Genome Biol Dept, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, CSIC,Univ Sevilla, Av Americo Vespucio, Seville 41092, Spain
Posavec-Marjanovic, M:
Germans Trias & Pujol Res Inst PMPPC IGTP, Program Predict & Personalized Med Canc, Badalona, Spain
Zarzuela, L:
Univ Pablo Olavide CSIC USE UPO, Cell Dynam & Signaling Dept, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, CSIC,Univ Sevilla, Av Americo Vespucio, Seville 41092, Spain
Basurto-Cayuela, L:
Univ Pablo Olavide CSIC USE UPO, Genome Biol Dept, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, CSIC,Univ Sevilla, Av Americo Vespucio, Seville 41092, Spain
Guerrero-Martinez, JA:
Univ Pablo Olavide CSIC USE UPO, Genome Biol Dept, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, CSIC,Univ Sevilla, Av Americo Vespucio, Seville 41092, Spain
Arribas, G:
Univ Pablo Olavide CSIC USE UPO, Genome Biol Dept, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, CSIC,Univ Sevilla, Av Americo Vespucio, Seville 41092, Spain
Yerbes, R:
Univ Pablo Olavide CSIC USE UPO, Cell Dynam & Signaling Dept, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, CSIC,Univ Sevilla, Av Americo Vespucio, Seville 41092, Spain
Ceballos-Chavez, M:
Univ Pablo Olavide CSIC USE UPO, Genome Biol Dept, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, CSIC,Univ Sevilla, Av Americo Vespucio, Seville 41092, Spain
Rodriguez-Paredes, M:
Johannes Gutenberg Univ Mainz, Univ Med Ctr Mainz, Inst Toxicol, D-55131 Mainz, Germany
Tome, M:
Univ Pablo Olavide CSIC USE UPO, Cell Dynam & Signaling Dept, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, CSIC,Univ Sevilla, Av Americo Vespucio, Seville 41092, Spain
Duran, RV:
Univ Pablo Olavide CSIC USE UPO, Cell Dynam & Signaling Dept, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, CSIC,Univ Sevilla, Av Americo Vespucio, Seville 41092, Spain
:
Germans Trias & Pujol Res Inst PMPPC IGTP, Program Predict & Personalized Med Canc, Badalona, Spain
Josep Carreras Leukaemia Res Inst IJC, Canc & Leukaemia Epigenet & Biol Program, Badalona 08916, Spain
Reyes, JC:
Univ Pablo Olavide CSIC USE UPO, Genome Biol Dept, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, CSIC,Univ Sevilla, Av Americo Vespucio, Seville 41092, Spain
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