Skeletrophin, a novel RING molecule controlled by the chromatin remodeling complex, is downregulated in malignant melanoma.
Recent experiments have revealed that aberrant functionality of the chromatin remodeling complex is related to tumorigenicity in various malignant tumors. Skeletrophin is an actin-binding cytoskeleton-related molecule, which is induced by the overexpression of truncated human SWI1 (SMARCF1). Human SWI1 is a sub-unit of the chromatin remodeling complex and binds chromatin through its ARID (AT-rich interactive domain). Truncated SWI1 lacks one of the two glucocorticoid-receptor binding domains and inhibits the intact human SWI1 in a dominant negative manner. Skeletrophin, was therefore identified as a candidate molecule for the indication of change to a malignant phenotype due to the aberrant function of the chromatin remodeling complex. Surprisingly, the skeletrophin gene is located in 1p36.32, where the putative tumor suppressor gene of cutaneous malignant melanoma has long been postulated to be on. Cutaneous malignant melanoma is a highly aggressive tumor. To overcome the clinical problem of malignant melanoma and highly invasive and metastatic activity, it is important to unravel the molecular mechanism responsible for melanoma progression. Recent studies including those from our laboratories have elucidated that skeletrophin is a novel RING-HC type ubiquitin ligase and that the ubiquitin ligase pathway mediated by skeletrophin acts to oppose melanoma cell invasion. Here, we summarize the characterization of skeletrophin, with emphasis on its biological activity, the disruption of which is linked with melanoma progression.
Takeuchi
Tamotsu
T
Department of Pathology, Kochi Medical School, Kochi 783-8505, Japan.
Adachi
Yoshihiro
Y
Ohtsuki
Yuji
Y
D002843:Chromatin / Q000378:metabolism*; D002878:Chromosomes, Human, Pair 1; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
D002843:Chromatin; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C478156:MIB2 protein, human; D044767:Ubiquitin-Protein Ligases