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General Comment |
Regulates Hippo signaling through de-phosphorylation...
Alveolar rhabdomyosarcomaassociated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression JCI 2014
Lisa E.S. Crose1, Kathleen A. Galindo2, Julie Grondin Kephart3, Candy Chen1, Julien Fitamant4, Nabeel Bardeesy4, Rex C. Bentley5, Rene L. Galindo2,6,7, Jen-Tsan Ashley Chi8,9 and Corinne M. Linardic1,3
NCBI Summary:
This gene encodes a protein similar to the RAS effector proteins. Loss or altered expression of this gene has been associated with the pathogenesis of a variety of cancers, which suggests the tumor suppressor function of this gene. The inactivation of this gene was found to be correlated with the hypermethylation of its CpG-island promoter region. The encoded protein was found to interact with DNA repair protein XPA. The protein was also shown to inhibit the accumulation of cyclin D1, and thus induce cell cycle arrest. Several alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, May 2011]
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Comment |
RASSF1A Regulates Spindle Organization by Modulating Tubulin Acetylation via SIRT2 and HDAC6 in Mouse Oocytes. Jeon HJ et al. (2020) Dynamic changes in microtubules during cell cycle progression are essential for spindle organization to ensure proper segregation of chromosomes. There is growing evidence that post translational modifications of tubulins are the key factors that contribute to microtubule dynamics. However, how dynamic properties of microtubules are regulated in mouse oocytes is unclear. Here, we show that tumor suppressor RASSF1A is required for tubulin acetylation by regulating SIRT2 and HDAC6 during meiotic maturation in mouse oocytes. We found that RASSF1A was localized at the spindle microtubules in mouse oocytes. Knockdown of RASSF1A perturbed meiotic progression by impairing spindle organization and chromosome alignment. Moreover, RASSF1A knockdown disrupted kinetochore-microtubule (kMT) attachment, which activated spindle assembly checkpoint and increased the incidence of aneuploidy. In addition, RASSF1A knockdown decreased tubulin acetylation by increasing SIRT2 and HDAC6 levels. Notably, defects in spindle organization and chromosome alignment after RASSF1A knockdown were rescued not only by inhibiting SIRT2 or HDAC6 activity, but also by overexpressing acetylation mimicking K40Q tubulin. Therefore, our results demonstrated that RASSF1A regulates SIRT2- and HDAC6-mediated tubulin acetylation for proper spindle organization during oocyte meiotic maturation.//////////////////
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