FERMT2

Abstract: Molecules involved in WNT/β-catenin signaling show spatiotemporal-specific expression and play vital roles in muscle development. Our previous study showed that WNT/β-catenin signaling promotes myoblast proliferation and differentiation through the regulation of the cyclin A2 (Ccna2)/cell division cycle 25C (Cdc25c) and Fermitin family homolog 2 (Fermt2) genes, respectively. However, it remains unclear how β-catenin targets different genes from stage to stage during myogenesis. Here, we show that the accessibility of β-catenin to the promoter region of its target genes is regulated by developmental stage-specific histone acetyltransferases (HATs), lysine acetyltransferase 2B (KAT2B), and cAMP-response element-binding protein (CREB)-binding protein (CBP). We found that KAT2B was specifically expressed at the myoblast proliferation stage and formed a complex with β-catenin to induce Ccna2/Cdc25c expression. On the other hand, CBP was specifically expressed during myoblast differentiation and formed a complex with β-catenin to induce Fermt2 expression. Our findings indicate that β-catenin efficiently accesses to its target gene's promoters by forming a complex with developmental stage-specific acetyltransferases during myogenesis.

Abstract: Alterations of cell mechano-environment and metabolism are common features of malignant neoplasm. We recently showed that increased stiffness of extracellular matrix is intrinsically linked to up-regulation of proline synthesis through a mechano-responsive fermitin family homolog 2 (FERMT2, best known as kindlin-2) and pyrroline-5-carboxylate reductase 1(PYCR1) complex, which in turn promotes collagen matrix synthesis, cell proliferation, survival, and cancer progression.