Entity

Time filter

Source Type


Hou H.,CAS Institute of Biophysics | Wang F.,Anhui Key Laboratory for Cellular Dynamics and Chemical Biology | Zhang W.,CAS Institute of Biophysics | Wang D.,Anhui Key Laboratory for Cellular Dynamics and Chemical Biology | And 5 more authors.
Journal of Biological Chemistry | Year: 2011

The cold shock domain (CSD) is an evolutionarily conserved nucleic acid binding domain that exhibits binding activity to RNA, ssDNA, and dsDNA. Mammalian CRHSP-24 contains CSD, but its structure-functional relationship has remained elusive. Here we report the crystal structure of human CRHSP-24 and characterization of the molecular trafficking of CRHSP-24 between stress granules and processing bodies in response to oxidative stress. The structure of CRHSP-24 determined by single-wavelength anomalous dispersion exhibits an α-helix and a compact β-barrel formed by five curved anti-parallel β strands. Ligand binding activity of the CSD is orchestrated by residues Ser41 to Leu43. Interestingly, a phosphomimetic S41D mutant abolishes the ssDNA binding in vitro and causes CRHSP-24 liberated from stress granules in vivo without apparent alternation of its localization to the processing bodies. This new class of phosphorylation-regulated interaction between the CSD and nucleic acids is unique in stress granule plasticity. Importantly, the association of CRHSP-24 with stress granules is blocked by PP4/ PP2A inhibitor calyculin A as PP2A catalyzes the dephosphorylation of Ser 41 of CRHSP-24. Therefore, we speculate that CRHSP-24 participates in oxidative stress response via a dynamic and temporal association between stress granules and processing bodies. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc. Source


Zhao L.,Anhui Key Laboratory for Cellular Dynamics and Chemical Biology | Jin C.,Anhui Key Laboratory for Cellular Dynamics and Chemical Biology | Chu Y.,Anhui Key Laboratory for Cellular Dynamics and Chemical Biology | Varghese C.,Morehouse School of Medicine | And 12 more authors.
Journal of Biological Chemistry | Year: 2010

Centrosome cohesion and segregation are accurately regulated to prevent an aberrant separation of duplicated centrosomes and to ensure the correct formation of bipolar spindles by a tight coupling with cell cycle machinery. CPAP is a centrosome protein with five coiled-coil domains and plays an important role in the control of brain size in autosomal recessive primary microcephaly. Previous studies showed that CPAP interacts with tubulin and controls centriole length. Here, we reported that CPAP forms a homodimer during interphase, and the fifth coiled-coil domain of CPAP is required for its dimerization. Moreover, this self-interaction is required for maintaining centrosome cohesion and preventing the centrosome from splitting before the G2/M phase. Our biochemical studies show that CPAP forms homodimers in vivo. In addition, both monomeric and dimeric CPAP are required for accurate cell division, suggesting that the temporal dynamics of CPAP homodimerization is tightly regulated during the cell cycle. Significantly, our results provide evidence that CPAP is phosphorylated during mitosis, and this phosphorylation releases its intermolecular interaction. Taken together, these results suggest that cell cycle-regulated phosphorylation orchestrates the dynamics of CPAP molecular interaction and centrosome splitting to ensure genomic stability in cell division. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Source


Mo F.,Anhui Key Laboratory for Cellular Dynamics and Chemical Biology | Mo F.,Hefei University of Technology | Zhuang X.,Anhui Key Laboratory for Cellular Dynamics and Chemical Biology | Zhuang X.,Hefei University of Technology | And 51 more authors.
Nature Chemical Biology | Year: 2016

Faithful segregation of chromosomes in mammalian cells requires bi-orientation of sister chromatids, which relies on the sensing of correct attachments between spindle microtubules and kinetochores. Although the mechanisms underlying cyclin-dependent kinase 1 (CDK1) activation, which triggers mitotic entry, have been extensively studied, the regulatory mechanisms that couple CDK1-cyclin B activity to chromosome stability are not well understood. Here, we identified a signaling axis in which Aurora B activity is modulated by CDK1-cyclin B via the acetyltransferase TIP60 in human cell division. CDK1-cyclin B phosphorylates Ser90 of TIP60, which elicits TIP60-dependent acetylation of Aurora B and promotes accurate chromosome segregation in mitosis. Mechanistically, TIP60 acetylation of Aurora B at Lys215 protects Aurora B's activation loop from dephosphorylation by the phosphatase PP2A to ensure a robust, error-free metaphase-anaphase transition. These findings delineate a conserved signaling cascade that integrates protein phosphorylation and acetylation with cell cycle progression for maintenance of genomic stability. © 2016 Nature America, Inc. Source


Chu L.,Anhui Key Laboratory for Cellular Dynamics and Chemical Biology | Huo Y.,Anhui Key Laboratory for Cellular Dynamics and Chemical Biology | Liu X.,Anhui Key Laboratory for Cellular Dynamics and Chemical Biology | Liu X.,Morehouse School of Medicine | And 16 more authors.
Journal of Biological Chemistry | Year: 2014

Background: HP1α is a heterochromatin protein essential for chromosome plasticity in mitosis.Results: HP1α localization to the centromere depends on two distinct structural determinants in interphase and mitotic cells.Conclusion: The centromere localization of HP1α is determined by its binding to H3K9me2/3 in interphase but to PXVXL motifs in mitosis.Significance: The context-dependent spatiotemporal dynamics of HP1α is essential for accurate mitosis. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Source


Yu J.,Zhejiang University | Yu J.,Anhui Key Laboratory for Cellular Dynamics and Chemical Biology | Lan J.,Zhejiang University | Lan J.,Anhui Key Laboratory for Cellular Dynamics and Chemical Biology | And 7 more authors.
Cancer Letters | Year: 2010

Telomerase-negative cancer cells maintain their telomeres by a mechanism known as alternative lengthening of telomeres (ALT) and achieve unlimited replicative potential. A hallmark of ALT cells is the recruitment of telomeres to promyelocytic leukemia (PML) bodies and formation of ALT-associated PML bodies (APBs). Although the exact molecular mechanism of APBs assembly remains unclear, APBs assembly requires telomere and PML body-associated proteins, including TRF1 and PML. Here, we report that PML3, one of PML isoforms, is involved in APBs formation. As a new binding protein of TRF1 (telomeric repeat binding factor 1), PML3 directly interacts with TRF1 and recruits TRF1 to PML bodies in U2OS cells. More notably, depletion of PML3 by small interfering RNA does not affect PML bodies formation, but inhibits the recruitment of both TRF1 and TRF2 to APBs. Further study shows that the recruitment of TRF1 to APBs depends on its interaction with a specific PML3 isoform. Thus, the interaction of PML3 with TRF1 is isoform specific and likely to be essential for APBs assembly in U2OS cells. © 2009 Elsevier Ireland Ltd. All rights reserved. Source

Discover hidden collaborations