Macrophage-erythroblast attacher E3 ubiquitin-protein ligase (MAEA)

Macrophage-erythroblast attacher E3 ubiquitin-protein ligase (MAEA) is a membrane-associated, RING domain-containing E3 ubiquitin ligase essential for hematopoietic stem cell maintenance, quiescence, and proper lymphoid potential[3]. It regulates degradation of cell-surface cytokine receptors (including FLT3 and MPL), thereby restricting intracellular cytokine signaling and maintaining stem cell autophagy flux. MAEA loss in mice leads to stem cell hyperactivation, severe hematopoietic abnormalities, and myeloproliferative syndromes[3]. MAEA also acts in macrophages to promote phagocytosis and modulate innate immune function by targeting substrates such as PARP1 for degradation[4]. MAEA’s E3 ligase activity is mechanistically tied to the CTLH complex, though its full set of interacting partners and substrates in human disease are still being elucidated[3]. Pharmacologic inhibition of receptor tyrosine kinases can partially rescue the effects of MAEA depletion, highlighting therapeutic intersections in diseases of blood and immune dysfunction[3]. This profile is based primarily on current molecular and disease biology literature; no approved drugs are known to directly target MAEA, but key roles in receptor turnover and autophagy position it as a potentially druggable node in hematologic and stem cell pathologies[3][4].

Other names

Macrophage-erythroblast attacherEMP (Erythroblast macrophage protein)MAEA

Promotion of polyubiquitination (especially Lys48/K48-linked chains) on substrate proteins such as cytokine receptors, targeting them for proteasomal degradation. Downregulation of cytokine/RTK signaling via receptor turnover (e.g., FLT3 degradation inhibits excess signaling). Upregulation of autophagy to modulate receptor and protein turnover in HSCs. Promotion of phagocytosis in macrophages (via ubiquitination of specific substrates such as PARP1).