PPARGC1A and cancer: TWIST1 is a helix-loop-helix–containing TF involved in early development, apoptosis, cancer, and osteoblast differentiation.93, –95 TWIST1 is also reported to downregulate the expression of PGC-1α in epithelial cells96 and skeletal muscle cells.97 Therefore, we propose that WWP2 is recruited to a transcriptional complex involving TWIST1 and that the complex binds to the regulatory locus of Ppargc1a.