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Fig. 2. Proteolytic processing of CD44. The extracellular stem region of CD44 is proteolytically cleaved by MT1- and MT3-MMPs in addition to other CD44 sheddases, leaving a CD44 C-terminal fragment (CTF) embedded in the plasma membrane. The cleaved extracellular region is either secreted into the fluid phase or sequestered to the extracellular matrix. Extracellular domain cleavage is necessary for further processing of the CD44-CTF by regulated intramembranous proteolysis (RIP) by presenilin-1/{gamma}-secretase activity. RIP processing results in the secretion of a CD44ß-like peptide and the generation of a CD44 intracellular domain fragment (ICD). The CD44-ICD has been shown to be involved in nuclear signalling.





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