Anti-MITF monoclonal antibody, clone 32E2529

Interrupted dimeric coiled coil segments are found in a broad range of proteins and generally confer selective functional properties such as binding to specific ligands. However, there is only one documented case of a basic-helix-loop-helix leucine zipper transcription factor-microphthalmia-associated transcription factor (MITF)-in which an insertion of a three-residue stammer serves as a determinant of conditional partner selectivity. To unravel the molecular principles of this selectivity, we have analyzed the high-resolution structures of stammer-containing MITF and an engineered stammer-less MITF variant, which comprises an uninterrupted symmetric coiled coil. Despite this fundamental difference, both MITF structures reveal identical flanking in-phase coiled coil arrangements, gained by helical over-winding and local asymmetry in wild-type MITF across the stammer region. These conserved structural properties allow the maintenance of a proper functional readout in terms of nuclear localization and binding to specific DNA-response motifs regardless of the presence of the stammer. By contrast, MITF heterodimer formation with other bHLH-Zip transcription factors is only permissive when both factors contain either the same type of inserted stammer or no insert. Our data illustrate a unique principle of conditional partner selectivity within the wide arsenal of transcription factors with specific partner-dependent functional readouts.

Clear cell sarcoma (CCS) is arare soft tissue tumor derived from neural crest cells. It accounts for 1% of all soft tissue sarcomas and usually involves the tendons and aponeuroses in the distal ends of the extremities. The foot and the ankle are the most common primary sites. A CCS predominantly occurs in young adults and has rarely been reported in children and older people. On magnetic resonance imaging the tumor has abenign appearance. It appears isointense, hypointense or slightly hyperintense on T1-weighted images. A CCS is typically strongly positive for HMB-45, S-100, melanA, MITF and vimentin on immunohistochemical investigations and exhibits the t(12;22)(q13;q12) translocation on cytogenetic studies. Metastasis occurs mainly to the regional lymph nodes. Atumor size 5cm is invariably associated with apoor prognosis. The main treatment is wide excision but local recurrence and distant metastases are common. This article presents the case of a61-year-old man with right ankle tenderness and malaise. Ultrasound-guided biopsy and pathological examination were performed and the pathological diagnosis was a CCS. The patient underwent abelow-knee amputation and had no local recurrence or metastasis at the 6-month follow-up.