Elucidation of Melanogenesis Cascade for Identifying Pathophysiology and Therapeutic Approach of Pigmentary Disorders and Melanoma

• Published in: International journal of molecular sciences Vol. 21; no. 17; p. 6129
• Main Authors: Hida, Tokimasa, Kamiya, Takafumi, Kawakami, Akinori, Ogino, Jiro, Sohma, Hitoshi, Uhara, Hisashi, Jimbow, Kowichi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.08.2020; MDPI
• Subjects: Albinism; Amino acids; Autocrine signalling; Biological activity; Biosynthesis; Cell Differentiation; Differentiation; Enzymes; eumelanin; Gene expression; Genes; Hair; Homeostasis; Humans; Keratinocytes; Kinases; Melanin; Melanins - metabolism; Melanocytes; Melanocytes - cytology; Melanocytes - metabolism; melanogenesis; Melanoma; Melanoma - drug therapy; Melanoma - metabolism; melanosome; Melanosomes; Microphthalmia-associated transcription factor; Microphthalmia-Associated Transcription Factor - metabolism; Mutation; Paracrine signalling; Pathophysiology; Phenotypes; Pheomelanin; Pigmentation; Pigmentation Disorders - drug therapy; Pigmentation Disorders - metabolism; Proteins; Review; Skin; Stem cells; Sunburn & sun tanning; Transcription factors; Tyrosinase; tyrosinase related protein (TYRP); Tyrosine; vesicular transport; pigment-type switching; pheomelanin; tyrosinase related protein (TYRP); hypomelanosis; melanosome; melanogenesis; melanoma; tyrosinase; eumelanin; vesicular transport
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21176129

Melanogenesis is the biological and biochemical process of melanin and melanosome biosynthesis. Melanin is formed by enzymic reactions of tyrosinase family proteins that convert tyrosine to form brown-black eumelanin and yellow-red pheomelanin within melanosomal compartments in melanocytes, following the cascades of events interacting with a series of autocrine and paracrine signals. Fully melanized melanosomes are delivered to keratinocytes of the skin and hair. The symbiotic relation of a melanocyte and an associated pool of keratinocytes is called epidermal melanin unit (EMU). Microphthalmia-associated transcription factor (MITF) plays a vital role in melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes for promoting melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis. Diseases involving alterations of EMU show various forms of pigmentation phenotypes. This review introduces four major topics of melanogenesis cascade that include (1) melanocyte development and differentiation, (2) melanogenesis and intracellular trafficking for melanosome biosynthesis, (3) melanin pigmentation and pigment-type switching, and (4) development of a novel therapeutic approach for malignant melanoma by elucidation of melanogenesis cascade.