Publications by authors named "Wei-Hao Shang"
Article Synopsis
- Most eukaryotic centromeres exist in heterochromatic areas, but this type of chromatin can sometimes hinder centromere development, leading to some centromeres lacking heterochromatin completely.
- Researchers engineered a synthetic human artificial chromosome (HAC) to study heterochromatin's role and used a demethylase to remove a specific heterochromatin mark from the HAC's centromere, which initially didn't cause any short-term issues.
- Long-term removal of this mark decreased critical centromere proteins, causing problems like incorrect chromosome segregation, but with some resilience allowing centromere function to adapt to different chromatin environments, suggesting that a minimal level of heterochromatin is essential for proper centromere
Article Synopsis
- CENP-A is crucial for defining and maintaining centromeres through the action of the Mis18 complex in chicken DT40 cells.
- The localization of the Mis18 complex to the centromere relies on CENP-A, rather than CENP-C or CENP-T.
- M18BP1/KNL2 is vital for centromere formation as it directly interacts with the CENP-A nucleosome, providing insights into how centromere positioning is recognized in non-mammalian vertebrates.
Centromeres are specified epigenetically through the deposition of the centromere-specific histone H3 variant CENP-A. However, how additional epigenetic features are involved in centromere specification is unknown. Here, we find that histone H4 Lys5 and Lys12 acetylation (H4K5ac and H4K12ac) primarily occur within the pre-nucleosomal CENP-A-H4-HJURP (CENP-A chaperone) complex, before centromere deposition.
View Article and Find Full Text PDFIn vertebrate cells, centromeres are specified epigenetically through the deposition of the centromere-specific histone CENP-A. Following CENP-A deposition, additional proteins are assembled on centromeric chromatin. However, it remains unknown whether additional epigenetic features of centromeric chromatin are required for kinetochore assembly.
View Article and Find Full Text PDFCentromeres are specified by sequence-independent epigenetic mechanisms in most organisms. Rarely, centromere repositioning results in neocentromere formation at ectopic sites. However, the mechanisms governing how and where neocentromeres form are unknown.
View Article and Find Full Text PDFCENP-A acts as an important epigenetic marker for kinetochore specification. However, the mechanisms by which CENP-A is incorporated into centromeres and the structural basis for kinetochore formation downstream of CENP-A remain unclear. Here, we used a unique chromosome-engineering system in which kinetochore proteins are targeted to a noncentromeric site after the endogenous centromere is conditionally removed.
View Article and Find Full Text PDFThe centromere is essential for faithful chromosome segregation by providing the site for kinetochore assembly. Although the role of the centromere is conserved throughout evolution, the DNA sequences associated with centromere regions are highly divergent among species and it remains to be determined how centromere DNA directs kinetochore formation. Despite the active use of chicken DT40 cells in studies of chromosome segregation, the sequence of the chicken centromere was unclear.
View Article and Find Full Text PDFKinetochore specification and assembly requires the targeted deposition of specialized nucleosomes containing the histone H3 variant CENP-A at centromeres. However, CENP-A is not sufficient to drive full-kinetochore assembly, and it is not clear how centromeric chromatin is established. Here, we identify CENP-W as a component of the DNA-proximal constitutive centromere-associated network (CCAN) of proteins.
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- Emerging research highlights the significant role of Nox1-generated reactive oxygen species (ROS) in regulating various cellular processes, although specific targets of Nox1 are still not well understood.
- The study identified ERp72, a protein with TRX homology domains, as a direct target of Nox1-induced oxidation, which leads to decreased reductase activity of ERp72.
- The findings show that Nox1 interacts with ERp72 at the plasma membrane, suggesting a functional partnership that influences redox-sensitive signaling pathways within cells.
Article Synopsis
- Reactive oxygen species (ROS) generated by the Nox1 enzyme are crucial for the transformation of normal cells into cancerous cells initiated by the Ras oncogene, affecting growth and morphology.
- The study reveals that in K-Ras-transformed cells, Rho activity is unexpectedly inactivated, which can be reversed by inhibiting Nox1-generated ROS, indicating that these oxidants interfere with Rho signaling.
- The mechanism involves the oxidative inactivation of a phosphatase, leading to increased levels of an active form of p190RhoGAP, which subsequently disrupts actin stress fibers and focal adhesions in transformed cells.
Amphiphysin1, which can simultaneously bind to dynamin1 and the clathrin adaptor AP-2, is essential for dynamin1 recruitment during receptor-mediated endocytosis, but little is known about its regulatory mechanism. Here, we purified a 120-kDa mitogen-activated protein kinase (MAPK) substrate protein from porcine brains and identified the protein as amphiphysin1. Serine phosphorylation of amphiphysin1 was rapidly induced by nerve growth factor (NGF) in PC12 cells, and the induction was blocked by a MAPK inhibitor.
View Article and Find Full Text PDFA 19 kDa protein was identified to associate with the Dbl oncogene homology domain of Sos1 (Sos-DH) and was purified from rat brains by GST-Sos-DH affinity chromatography. Peptide sequencing revealed that the protein is identical to light chain 3 (LC3), a microtubule-associated protein. LC3 coimmunoprecipitated with Sos1, and GST-LC3 was capable of forming complexes with Sos1 in in vitro GST-pull down assay.
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