20 research outputs found
Dual Chromatin and Cytoskeletal Remodeling by SETD2
Posttranslational modifications (PTMs) of tubulin specify microtubules for specialized cellular functions and comprise what is termed a "tubulin code." PTMs of histones comprise an analogous "histone code," although the "readers, writers, and erasers" of the cytoskeleton and epigenome have heretofore been distinct. We show that methylation is a PTM of dynamic microtubules and that the histone methyltransferase SET-domain-containing 2 (SETD2), which is responsible for H3 lysine 36 trimethylation (H3K36me3) of histones, also methylates α-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy. These data now identify SETD2 as a dual-function methyltransferase for both chromatin and the cytoskeleton and show a requirement for methylation in maintenance of genomic stability and the integrity of both the tubulin and histone codes
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A TSC signaling node at the peroxisome regulates mTORC1 and autophagy in response to ROS
Subcellular localization is emerging as an important mechanism for mTORC1 regulation. We report that the tuberous sclerosis complex (TSC) signaling node, TSC1, TSC2 and Rheb, localizes to peroxisomes, where it regulates mTORC1 in response to reactive oxygen species (ROS). TSC1 and TSC2 were bound by PEX19 and PEX5, respectively, and peroxisome-localized TSC functioned as a Rheb GAP to suppress mTORC1 and induce autophagy. Naturally occurring pathogenic mutations in TSC2 decreased PEX5 binding, abrogated peroxisome localization, Rheb GAP activity, and suppression of mTORC1 by ROS. Cells lacking peroxisomes were deficient in mTORC1 repression by ROS and peroxisome-localization deficient TSC2 mutants caused polarity defects and formation of multiple axons in neurons. These data identify a role for TSC in responding to ROS at the peroxisome, and identify the peroxisome as a signaling organelle involved in regulation of mTORC1
Methylated α-tubulin antibodies recognize a new microtubule modification on mitotic microtubules
Le Bulletin de Vouziers : journal politique, industriel et agricole de l'arrondissement, paraissant toutes les semaines
14 février 18861886/02/14 (N219)-1886/02/14.Appartient à l’ensemble documentaire : ChArdenn
HL60 (A) or OCI-AML3 cells stably expressing shRNA silencing p53 (B) were treated with Nutlin 3a for 24–96 hrs and analyzed by flow cytometry for AnnV/MDC staining.
<p>HL60 (A) or OCI-AML3 cells stably expressing shRNA silencing p53 (B) were treated with Nutlin 3a for 24–96 hrs and analyzed by flow cytometry for AnnV/MDC staining.</p
OCI-AML3 cells transduced with LC3-GFP-mCherry construct were treated with 5 μM Nutlin 3a and visualized by confocal microscopy.
<p>Increase in proportion of red ‘puncta’ at 96 hrs compared to 48 hrs (merge images) in Nutlin 3a treated cells indicate completion of autophagic flux.</p