Domain structures of mucosa-associated lymphoid tissue lymphoma translocation 1 protein for nuclear localization in oral carcinoma cells and the proliferation inhibition

Abstract

Mucosa-associated lymphoid tissue lymphoma translocation 1 protein (MALT1) consisting of death domain, Ig-like domains and caspase-like domain is expressed in nucleus of oral carcinoma cells, and loss of the expression closely associates with disease progression and stimulates proliferation of the cells. However, nothing is known about the molecular backgrounds. In this study, eight constructs with different domain constitution of human MALT1 and six constructs were transiently and stably transfected into oral carcinoma cell lines, respectively. The immunoblot analysis showed that constructs containing caspase-like domain was expressed in nucleus and the domain-deleted constructs in cytoplasm. Immunocytochemistry of stably transfected HSC2 oral carcinoma cells confirmed the caspase-like domain-dependent nuclear localization. Involvement of domains in proliferation of stably transfected HSC2 cells was quantified by the real-time and conventional colorimetric assays. In contrast to suppression of the proliferation by full-length wild-type MALT1, any domain-deleted constructs enhanced the proliferation. Death domain construct without caspase-like domain suppressed the proliferation when it was localized in nucleus by ligating with the nuclear localization signal. These results demonstrate that nuclear localization of MALT1 in oral carcinoma cells depends on the presence of caspase-like domain and that death domain nuclear entity is responsible for MALT1 inhibition of oral carcinoma cell proliferation. Nuclear localization of death domain led by caspase-like domain may suppress oral carcinoma progression.