Endothelial monocyte-activating polypeptide II (EMAP-II)

Endothelial monocyte-activating polypeptide II (EMAP-II) is a multifunctional cytokine that plays a critical role in inflammation, angiogenesis, and apoptosis. It is generated by the proteolytic cleavage of its precursor, aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (AIMP1), which is a scaffold protein in the multisynthetase complex involved in protein translation. EMAP-II is released from cells in response to stress, hypoxia, or apoptosis and acts as a potent chemoattractant for monocytes and neutrophils. In the context of cancer, EMAP-II exhibits anti-angiogenic properties by inducing apoptosis in growing endothelial cells and sensitizing the tumor vasculature to tumor necrosis factor-alpha (TNF-alpha). Conversely, in chronic inflammatory lung diseases like pulmonary arterial hypertension (PAH) and viral-induced lung injury, elevated EMAP-II levels contribute to pathological remodeling and inflammation, making it a target for inhibitory monoclonal antibodies. Therapeutic development includes recombinant EMAP-II for cancer treatment and anti-EMAP-II antibodies for cardiopulmonary disorders.

Other names

AIMP1p43SCYE1EMAP2Small inducible cytokine subfamily E member 1Aminoacyl tRNA synthase complex-interacting multifunctional protein 1Multisynthetase complex auxiliary component p43

Drugs targeting EMAP-II utilize different mechanisms depending on the therapeutic goal. Recombinant EMAP-II acts as an anti-angiogenic agent by binding to the alpha subunit of ATP synthase on endothelial cells, leading to apoptosis and sensitization of the tumor vasculature to TNF-alpha. It also induces autophagy and growth arrest in tumor cells via the PI3K/Akt/FoxO1 pathway. Conversely, therapeutic monoclonal antibodies aim to neutralize extracellular EMAP-II to prevent its pro-inflammatory and pro-apoptotic effects on the lung vasculature in diseases like pulmonary arterial hypertension and viral-induced lung injury.