A76-26 Nucleoporin 62 Regulates Proliferation of Human Airway Smooth Muscle Cells

Abstract Nucleoporin 62 (NUP62), a core component of the nuclear pore complex (NPC), regulates bidirectional transport of macromolecules across the nuclear envelope. Beyond its canonical transport role, NUP62 has been implicated in mitotic spindle organization and chromosome segregation in cancer cells, thereby promoting tumor cell proliferation. However, the function of NUP62 in human airway smooth muscle (HASM) cells remains unknown. Given that excessive airway smooth muscle cell proliferation contributes to airway remodeling in asthma, this study examined the role and mechanism of NUP62 in HASM cell proliferation. HASM cells were treated with control or NUP62 siRNA. Immunoblot analysis verified down-regulation of NUP62 in cells. Silencing NUP62 markedly suppressed DNA synthesis, assessed by BrdU incorporation, and reduced cell proliferation upon stimulation with platelet-derived growth factor (PDGF). Furthermore, NUP62 knockdown impaired PDGF-induced nuclear translocation of Signal Transducer and Activator of Transcription 3 (STAT3), a key transcription factor that promotes the proliferation of HASM cells. It is well accepted that protein acetylation is an important post-translational modification, which is important for the regulation of protein functions. Lysine 22 (K22) and Lysine 96 (K96) are located at the Phe-Gly (FG) domain of NUP62, which plays an essential role in nuclear cargo translocation. We have generated site-specific antibodies against acetylated K22 and acetylated K96. By using these two antibodies, we discovered that PDGF stimulation increased the acetylation of NUP62 at K22 and at K96. Taken together, these studies suggest that NUP62 regulates smooth muscle cell proliferation by controlling STAT3 nuclear translocation. Acetylation at K22 and K96 may involve the regulation of smooth muscle cell proliferation. Supported by NIH grant HL-130304 This abstract is funded by: NIH