Microphthalmia-Associated Transcription Factor in Senescence and Age-Related Diseases

Abstract

Although microphthalmia-associated transcription factor (MITF) has been known for decades as a key regulator for melanocytic differentiation, recent studies expanded its other roles in multiple biological processes. Among these newfound roles, the relationship between MITF and aging is attractive; however, the underlying mechanism remains elusive. Here, we review the documented cues that highlight the implication of MITF in the aging process and particularly discuss the possible mechanisms underlying the participation of MITF in cellular senescence. First, it summarizes the association of MITF with melanocytic senescence, including the roles of MITF in cell cycle regulation, DNA damage repair, oxidative stress response, and the generation of senescence-associated secretory phenotype. Then, it collects the information involving MITF-related senescent changes in nonmelanocytes, such as retinal pigment epithelium cells, osteoclasts, and cardiomyocytes. This review may deepen the understanding of MITF function and be helpful to develop new strategies for improving geriatric health.

Canonical Wnt and TGF-β/BMP signaling enhance melanocyte regeneration but suppress invasiveness, migration, and proliferation of melanoma cells

“…Whereas early regeneration was enriched for various types of DNA repair, including base excision, mismatch, and double-strand break, melanoma showed no enrichment for DNA repair pathways. This observation is also supported by the enrichment of the KEGG pathway called Fanconi anemia, which has been shown to promote homologous recombination upon DNA interstrand crosslinks by suppressing nucleotide-excision repair and is mainly deregulated in cancer predispositions (Michl et al, 2016;Fang et al, 2020;Zhang et al, 2021). Proper activation of DNA repair mechanisms is essential for homeostatic renewal and tissue regeneration following injury since defects in these mechanisms could interfere with the ability of adult stem cells to rebuild healthy tissues and increase the susceptibility to malignant transformations (Al Zouabi and Bardin, 2020).…”

Canonical Wnt and TGF-β/BMP signaling enhance melanocyte regeneration and suppress invasiveness, migration, and proliferation of melanoma cells

“…Whereas early regeneration was enriched for various types of DNA repair including base excision, mismatch and double strand break, melanoma showed no enrichment for DNA repair pathways. This is also supported by enrichment of the KEGG pathway called Fanconi anemia that has been shown to promote homologous recombination upon DNA interstrand crosslinks by suppressing nucleotide-excision repair and is mostly deregulated in cancer predispositions (Sancar and Tang 1993, Michl, Zimmer et al 2016, Fang, Wu et al 2020, Zhang, Mou et al 2021. Proper activation of DNA repair mechanisms is essential for homeostatic renewal and tissue regeneration following injury since defects in these mechanisms could interfere with the ability of adult stem cells to rebuild healthy tissues and increase the susceptibility of malignant transformations (Al Zouabi and Bardin 2020).…”

Reversing Gray Hair: Inspiring the Development of New Therapies Through Research on Hair Pigmentation and Repigmentation Progress

“…MITF is the positive regulator of anti-apoptotic factors B-cell-lymphoma 2 (BCL2) and baculoviral IAP repeat containing 7 (BIRC7) 62 , 63 and is involved in the regulation of the oncogenic hepatocyte growth factor receptor MET and the type III ribonuclease DICER, a necessary regulator of microRNA processing, thereby performing its anti-apoptotic effects 64 , 65 . It is widely thought that MITF mitigates DNA damage by increasing a group of repair genes, including DNA ligase I (LIG1), telomerase reverse transcriptase (TERT), essential meiotic endonuclease 1 homolog 1 (EME1), Breast Cancer 1 protein (BRCA1), and Fanconi anemia protein A (FANCA) 66 . MITF transcriptionally regulates General transcription factor IIH subunit 1 (GTF2H1), which encodes the core component of Transcription Factor IIH (TFIIH), and CDK7, which encodes TFIIH kinase to promote the rapid recovery of nucleotide excision repair 67 .…”