MARCH ubiquitin ligases alter the itinerary of clathrin-independent cargo from recycling to degradation

The MARCH family of proteins are membrane-associated E3 ubiquitin ligases that down-regulate surface membrane proteins. Expression of MARCH8 in cells causes the ubiquitination and down-regulation of surface CD98 and CD44—cargo proteins that enter cells by clathrin-independent endocytosis and are usually routed to recycling, not degradation.