Fig. 9
From: CDK6 inhibits white to beige fat transition by suppressing RUNX1
A working model of the role of CDK6 in negative regulation of white fat browning by suppressing RUNX1. In response to food intake, increased expression of cyclin D138 and CDK6 leads to activation of CDK6 (Supplementary Fig. 1). In addition, the canonical cascade of events is initiated, including the activation of Notch139 and AKT140. Notch1 activates CDK6 via upregulation of CDK6 and/or by increased cyclin D3 protein41. AKT1 activates CDK6 by stabilizing cyclin D242. Phosphorylation of RUNX1 by CDK6 and other kinases such as ERK and CDK110 promotes RUNX1 proteolytic degradation10, resulting in a reduction of RUNX1 recruitment to the proximal promoter regions of Ucp-1 and Pgc-1α (Supplementary Fig. 9), subsequently leading to reduced level of BAT-specific protein expression. In the absence of CDK6 protein/kinase activity, RUNX1 is stabilized, BAT-specific protein expression is increased, and obesity and its related metabolic diseases are suppressed
