【作者】 杨振业； 国静； 周绪斌； 王嵘； 朱学良；

【机构】 中国科学院上海生命科学研究院生物化学与细胞生物学研究所；

【摘要】 <正>Mitosin/CENP-F is a human nuclear matrix protein with multiple leucine zipper motifs. Its accumulation in S-G2 phases and transient kinetochore localization in mitosis suggest a multifunctional protein for cell proliferation,while its murine and avian orthologs are implicated in myocyte differentiation. We found that mitosin interacted with ATF4,a ubiquitous basic leucine-zipper transcription factor important for proliferation,differentiation, and stress response. Mitosin mutants containing the interaction domains were able to either supershift or disrupt the ATF4-DNA complex. Moreover, overexpression of full-length mitosin repressed the transactivation activity of ATF4 in dual luciferase-based reporter assays, while knocking down mitosin expression manifested the opposite effects. On the other hand, we showed that mitosin depletion attenuated chromosome congression and led to metaphase arrest with misaligned polar chromosomes. Kinetochores of fully aligned chromosomes often failed to show orientations in the direction of the spindle long axis. Moreover, tension across their sister kinetochores was decreased by half. Consistently, intensities of CENP-E and cytoplasmic dynein/dynactin, which are motors controlling microtubule attachment and chromosome movement, were reduced at the kinetochore in microtubule-dependent manners. These phenotypes collectively imply defects in motor functions in mitosin-depleted cells. In addition, mitosin-depleted mitotic cells were arrested in a pseudometaphase state and died through apoptosis after chromosome decondendation. Since mitosin is normally degraded at the end of mitosis when chromosome decondensation is about to occur for the nucleus reassembly, the premature chromosome decondensation in mitosin-depleted cells implies a role of mitosin in chromosome disassembly.更多还原