TY - JOUR
T1 - Microphthalmia-associated transcription factor (MITF)
T2 - Multiplicity in structure, function, and regulation
AU - Shibahara, Shigeki
N1 - Funding Information:
This work was supported in part by Grants-in-Aid for Encouragement of Young Scientists (to K. Y.), and for Scientific Research (B) from the Ministry of Education, Science, Sports, and Culture of Japan. This work was also supported in part by the Nakatomi Foundation and the Kao Foundation for Arts and Sciences.
PY - 2001
Y1 - 2001
N2 - Microphthalmia-associated transcription factor (MITF) regulates the differentiation and development of melanocytes and retinal pigment epithelium and is also responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Heterozygous mutations in the MITF gene cause auditorypigmentary syndromes. MITF consists of at least five isoforms, MITF-A, MITF-B, MITF-C, MITF-H, and MITF-M, differing at their N-termini and expression patterns. Here we show a remarkable similarity between the N-terminal domain of MITF-A and cytoplasmic retinoic acid-binding proteins. To date, four isoform-specific first exons have been identified in the MITF gene: exons 1A, 1H, 1B, and 1M in the 5′ to 3′ direction, each of which encodes the unique N-terminus of a given isoform. The 5′-flanking regions of these isoform-specific exons are termed A, H, B, and M promoters, respectively. Among these promoters, the M promoter has received particular attention, because it is functional only in melanocyte-lineage cells and is upregulated by Wnt signaling via the functional LEF-1-binding site. Moreover, the M promoter is upregulated by other transcription factors, PAX3, SOX10, and CREB. The activity and degradation of MITF-M are regulated by extracellular signals via protein phosphorylation, such as c-Kit signaling. Together, multiple signals appear to converge on the M promoter as well as on MITF proteins, leading to the proper regulation of MITF-M in melanocytes and other MITF isoforms in many cell types.
AB - Microphthalmia-associated transcription factor (MITF) regulates the differentiation and development of melanocytes and retinal pigment epithelium and is also responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Heterozygous mutations in the MITF gene cause auditorypigmentary syndromes. MITF consists of at least five isoforms, MITF-A, MITF-B, MITF-C, MITF-H, and MITF-M, differing at their N-termini and expression patterns. Here we show a remarkable similarity between the N-terminal domain of MITF-A and cytoplasmic retinoic acid-binding proteins. To date, four isoform-specific first exons have been identified in the MITF gene: exons 1A, 1H, 1B, and 1M in the 5′ to 3′ direction, each of which encodes the unique N-terminus of a given isoform. The 5′-flanking regions of these isoform-specific exons are termed A, H, B, and M promoters, respectively. Among these promoters, the M promoter has received particular attention, because it is functional only in melanocyte-lineage cells and is upregulated by Wnt signaling via the functional LEF-1-binding site. Moreover, the M promoter is upregulated by other transcription factors, PAX3, SOX10, and CREB. The activity and degradation of MITF-M are regulated by extracellular signals via protein phosphorylation, such as c-Kit signaling. Together, multiple signals appear to converge on the M promoter as well as on MITF proteins, leading to the proper regulation of MITF-M in melanocytes and other MITF isoforms in many cell types.
KW - Melanocyte
KW - Retinal pigment epithelium
KW - Retinoic acid
KW - Waardenburg syndrome
KW - Wnt signaling
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U2 - 10.1046/j.0022-202x.2001.00010.x
DO - 10.1046/j.0022-202x.2001.00010.x
M3 - Article
C2 - 11764295
AN - SCOPUS:0035513744
VL - 6
SP - 99
EP - 104
JO - Journal of Investigative Dermatology Symposium Proceedings
JF - Journal of Investigative Dermatology Symposium Proceedings
SN - 1087-0024
IS - 1
ER -