Modulation of cell surface density of carbonic anhydrase IX by shedding of the ectodomain and endocytosis

Carbonic anhydrase IX (CA IX) is a cell surface protein frequently present in human tumors but not in the corresponding normal tissues. Expression of CA IX is primarily determined by the strong transcriptional activation of the gene encoding CA IX by hypoxia via the hypoxia-inducible transcription factor HIF-1. However, the ultimate abundance of the CA IX protein on the cell surface can be affected by additional mechanisms, including ectodomain shedding and endocytosis. In this paper, we summarize the basic knowledge on how these processes modulate CA IX expression at the post-translational level. We propose that the regulation of the CA IX protein residence in the plasma membrane can influence its biological function as well as its clinical exploitation.