Regulatory role of transcription factor c-Myc in the pathogenesis of psoriasis

Abstract

Psoriasis is a chronic relapsing dermatosis characterized by hyperproliferation and poor differentiation of keratinocytes (KCs). The c-Myc gene is one of the main members of the Myc family and exerts multiple biological functions. C-Myc is highly expressed in psoriatic lesions. The co-expressed genes and coexisting factors of c-Myc determine the final survival of cells. The high expression levels of c-Myc in the skin lesions of psoriatic patients are associated with the continuous proliferation of KCs, and form an abnormal state of epidermal dynamics. C-Myc is also involved in the induction of metabolic reprogramming of cells in the development of psoriasis, thus exacerbating the excessive proliferation of psoriatic epidermis. In this review, we focus on the mechanisms of the transcription factor c-Myc in the pathogenesis of psoriasis and its clinical implications.

Keywords: Keratinocytes; Metabolic reprogramming; Proliferation; Psoriasis; c-Myc.

Figure 1. The structure of c-Myc.

C-Myc contains three structural domains: an N-terminal transcriptional activation domain (TAD), a non-specific DNA binding region, and a target sequence located at the C-terminal that binds to basic helix loop helix (bHLH) and leucine zipper (LZ) (Herbst et al., 2004).

Figure 2. Biological function of c-Myc.

The c-Myc protein encoded by the c-Myc gene can promote cell proliferation, inhibit stem cell differentiation, promote angiogenesis, interfere with cell apoptosis, and induce cell metabolic reprogramming and other basic biological activities.

Figure 3. The role of c-Myc in psoriasis.

The binding of IL-22 to the KC-specific receptor IL-22R induces the activation and phosphorylation of STAT3, and causes the overexpression of c-Myc, leading to excessive synthesis of GLUT1, resulting in an increased glycolysis and the induction of cell metabolism reprogramming in the development of psoriasis. Consequently, altered metabolism can cause the hyperproliferation of KC and abnormal proliferation of psoriatic epidermis.