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MARCH 1 regulates the IR: (a) MARCH 1 ubiquitinates and degrades the β-subunit of the IR, thereby decreasing IR surface expression; (b) IR activation inhibits FOXO, resulting in transcriptional repression of MARCH 1 and an increase in surface IR levels; (c) Insulin fails to inhibit FOXO, leading to enhanced MARCH 1 expression, reduced surface IR levels, and an impaired IIS pathway. Ub, ubiquitin. FOXO, forkhead transcription factor subgroup O.
