Journal of Clinical Immunology and Allergy

Mechanism of SIGIRR E8-Mediated ER Retention And Its Implications For Colorectal Tumor Progression

Colorectal cancer (CRC) is second most common cancer in Europe, with 450,000 new cases each year. A critical step in the pathogenesis of CRC is the inactivation of tumor suppressor genes. We have previously shown that the single immunoglobulin IL-1 receptor related molecule (SIGIRR) functions as a tumor suppressor in animal models of CRC. Recently, we have found that SIGIRR is frequently inactivated in human CRC by the increased expression of a novel SIGIRR isoform (SIGIRRΔE8), which is generated by an alternative splicing. SIGIRRΔE8 functions as a dominant negative mutant that inactivates the full-length SIGIRR protein by trapping it in the ER, via interaction with ER resident protein - ribophorin 1 (RPN1).

Author(s):

Malgorzata Bodaszewska Lubas

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