ISG15 and colorectal carcinoma: Using clones of CRC cells expressing the L1/H210Q and the L1/D598N point mutations in the L1 ectodomain that affect L1-L1 binding (H/210Q) and the binding of L1 to ECM components (L1/D598N), we found that such CRC cells display a much-reduced level of ISG15 (Figure 4A), suggesting that an unperturbed ectodomain binding of L1 with ligands outside the cell is necessary for propagating the downstream signaling that leads to increased ISG expression.