IndraLab

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TP53 activates MYSM1. 11 / 11
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"Our study also provides important insights into the unique effects of p53 stress responses in HSCs, where p53 activation in Mysm1 deficiency does not result in apoptosis, but promotes loss of quiescence."
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"To our knowledge, the role of p53 activation in Mysm1 deficient NK cell dysfunction has not been addressed [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"The suggested triggers for p53 activation in Mysm1 -/- include the putative roles of MYSM1 in the maintenance of p19ARF expression within the thymus [XREF_BIBR], and IRF2 and IRF8 expression in bone marrow progenitor cells [XREF_BIBR]."
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"XREF_BIBR, XREF_BIBR Importantly, Cdkn2a expression was undetectable in Mysm1 deficient HSPCs or MPPs, demonstrating the distinct mechanism of p53 activation in Mysm1 -/- HSPCs, as compared with thymocytes."
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"As increased p19 ARF / p53 activation in developing Mysm1 deficient mice could be a consequence of checkpoint activation, a default pathway, or be induced as a result of a lack of 2A-DUB/Mysm1 action in regulatory complexes involved in repression of the Cdkn2a (Ink4 and Arf) locus, we next set out to explore Mysm1 binding to fragments of the p19 ARF promoter in activated thymocytes."
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"As induction of Cdkn2a and p19 ARF was previously implicated in p53 activation in Mysm1 -/- thymocytes, 39 we conclude that the mechanisms of p53 activation in Mysm1 deficient HSPCs are distinct and p19 ARF -independent."
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"However, the mechanisms triggering p53 activation in Mysm1 -/- HSPCs, and the pathways downstream of p53 driving different aspects of the Mysm1 -/- phenotype remain unknown."
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"Using double-knockout mouse models, we establish that PUMA, but not p21, is an important mediator of p53 driven Mysm1 -/- hematopoietic dysfunction."
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"P53 mediates loss of hematopoietic stem cell function and lymphopenia in Mysm1 deficiency."
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"In summary, our results demonstrate novel roles for Mysm1 in osteoblast differentiation and osteoclast formation, resulting in osteopenia in Mysm1 deficient mice that could be abrogated by the loss of p53 from increased osteogenic differentiation of Mysm1 -/- p53 -/- MSCs.-Haffner-Luntzer, M., Kovtun, A., Fischer, V., Prystaz, K., Hainzl, A., Kroeger, C. M., Krikki, I., Brinker, T. J., Ignatius, A., Gatzka, M. Loss of p53 compensates osteopenia in murine Mysm1 deficiency."
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"Belle et al. 34 and Gatzka et al. 35 independently generated Mysm1 -/- p53 -/- mice that largely restored Mysm1 deficiency associated defects."
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