Leucine-rich repeats and immunoglobulin-like domain protein 1 in murine model of wound healing and p27 protein modeling

Abstract

Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) was first isolated by Nilsson in 2001 and since then its role as a tumor suppressor has been widely studied. In epithelial cancers, LRIG1 is known to suppress epidermal growth factor receptor’s (EGFR) downstream signaling. Moreover, mice deficient in LRIG-1 gene show histopathological features similar to psoriatic skin lesions. Therefore, we aimed to explore the LRIG-1 expression in full thickness epidermal excisional wound healing murine model. Female balb/c mice skin tissue sections were taken at day 1, 2, 3, 6 and day 14 after wounding. The highest expression of LRIG-1 was found to be expressed at day 0. There was a gradual decline in the LRIG-1 expression during the most of the wound healing stages. The regain of LRIG1 expression on day 14 marks the importance of LRIG1 in normal non-proliferative skin status or homeostasis. In addition to this, we used abinitio tools to model p27 protein also reported as a tumor suppressor protein often found to be down regulated in the EGFR over expressing epithelial cells. Novel mutations: c.4_6insGTT and c.520delA in p27 gene were reported by a previous colleague from our lab. These mutations can affect the post-translational modifications of the p27 proteins. Therefore, we were interested to explore the functional implications of these mutations. It was found that the novel mutation in p27 protein affects its interaction with AKT, furthermore, it was found that p27 nuclear localization was most likely to occur. Thus, this prediction model outlines few of the ways how p27 mutations may alter its function thus playing a possible pathogenic role in cancer progression.