Macrophage inhibitory cytokine-1 (Mic-1), also termed GDF15, PTGF-beta, PLAB, PDF, and NAG-1, is a divergent member of the transforming growth factor-beta (TGF-beta) superfamily. Like other family members, Mic-1 is synthesized as an inactive precursor that undergoes proteolytic processing involving removal of an N-terminal hydrophobic signal sequence followed by cleavage at a conserved RXXR site generating an active C-terminal domain that is secreted as a dimeric protein. Mic-1 is highly expressed in the placenta and is also dramatically increased by cellular stress, acute injury, inflammation, and cancer. In the brain, Mic-1 is found in the choroid plexus and is secreted into the cerebrospinal fluid. It is also a transcriptional target of the p53 tumor suppressor protein and may serve as a biomarker for p53 activity. During tumor progression, Mic-1 has various effects on apoptosis, differentiation, angiogenesis, and metastasis, and may also contribute to weight loss during cancer.
