MAPK-Activated Protein Kinase 2 Is Required for Mouse Meiotic Spindle Assembly and Kinetochore-Microtubule Attachment

MAPK-activated protein kinase 2 (MK2), a direct substrate of p38 MAPK, plays key roles in multiple physiological functions in mitosis. Here, we show for the first time the unique distribution pattern of MK2 in meiosis. Phospho-MK2 was localized on bipolar spindle minus ends and along the interstitial axes of homologous chromosomes extending over centromere regions and arm regions at metaphase of first meiosis (MI stage) in mouse oocytes. At metaphase of second meiosis (MII stage), p-MK2 was localized on the bipolar spindle minus ends and at the inner centromere region of sister chromatids as dots. Knockdown or inhibition of MK2 resulted in spindle defects. Spindles were surrounded by irregular nondisjunction chromosomes, which were arranged in an amphitelic or syntelic/monotelic manner, or chromosomes detached from the spindles. Kinetochore–microtubule attachments were impaired in MK2-deficient oocytes because spindle microtubules became unstable in response to cold treatment. In addition, homologous chromosome segregation and meiosis progression were inhibited in these oocytes. Our data suggest that MK2 may be essential for functional meiotic bipolar spindle formation, chromosome segregation and proper kinetochore–microtubule attachments

Autophagy: a new target for the treatment of salivary gland adenoid cystic carcinoma

This journal suppl. entitled: 22nd International Conference on Oral & Maxillofacial SurgeryPosterBACKGROUND: Our previous studies found that expression of Beclin 1 and other autophagy related genes in salivary gland adenoid cystic carcinoma (ACC) was lower than tumour-adjacent normal tissue. Beclin 1 protein and mRNA expression were independent prognostic factors for ACC patients. We hypothesized that autophagy may influence chemosensitivity and radiosensitivity of ACC. OBJECTIVES: To investigate the role of autophagy in radiotherapy and chemotherapy of salivary gland ACC. METHODS: The autophagy level and the expression of Beclin 1 were investigated when ACC cells treated with Obatoclax, Cisplatin, radiation, or Cisplatin+ radiation. Then the cytotoxicity was evaluated when down-regulating or up-regulating expression of Beclin 1, with or without pharmacologically inhibiting autophagy level or apoptosis activity. FINDINGS: Obatoclax increased autophagy level and expression of Beclin 1 in ACC cells. These effects were suppressed by 3-MA or CQ. Autophagy level was decreased when suppressing Beclin 1 expression. When autophagy was suppressed by Beclin 1 shRNA, 3-MA or CQ, sensitivity to Cisplatin of ACC cells was significantly increased. However radiosensitivity of cells decreased when autophagy was suppressed. CONCLUSIONS: Autophagy participates in responding to chemotherapy and radiation of human salivary gland ACC cells. Regulation of autophagy level can influence chemosensitivity and radiosensitivity of ACC cells. These findings indicated regulating of autophagy would be a new therapeutic strategy for salivary gland ACC. The project was supported by Seed Funding Programme for Basic Research, the University of Hong Kong (No. 201501159006)

Improvement on hydrogen generation properties of Zr(BH₄)₄·8NH₃

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