The Experts below are selected from a list of 5709 Experts worldwide ranked by ideXlab platform
Junmin Peng - One of the best experts on this subject based on the ideXlab platform.
-
the u4 u6 recycling factor sart3 has histone chaperone activity and associates with usp15 to regulate h2b Deubiquitination
Journal of Biological Chemistry, 2014Co-Authors: Lindsey Long, Joseph P Thelen, Melonnie Furgason, Mahmood Hajyahya, Ashraf Brik, Dongmei Cheng, Junmin PengAbstract:Post-translational modifications of histone proteins produce dynamic signals that regulate the structure and function of chromatin. Mono-ubiquitination of H2B in the histone tail (at Lys-123 in yeast or Lys-120 in humans) is a conserved modification that has been implicated in the regulation of transcription, replication, and DNA repair processes. In a search for direct effectors of ubH2B, we identified a deubiquitinating enzyme, Usp15, through affinity purification with a nonhydrolyzable ubH2B mimic. In the nucleus, Usp15 indirectly associates with the ubH2B E3 ligase, RNF20/RNF40, and directly associates with a component of the splicing machinery, SART3 (also known as TIP110 or p110). These physical interactions place Usp15 in the vicinity of actively transcribed DNA. Importantly we found that SART3 has previously unrecognized histone chaperone activities. SART3, but not the well-characterized histone chaperone Nap1, enhances Usp15 binding to ubH2B and facilitates Deubiquitination of ubH2B in free histones but not in nucleosomes. These results suggest that SART3 recruits ubH2B, which may be evicted from DNA during transcription, for Deubiquitination by Usp15. In light of the function played by SART3 in U4/U6 di-snRNP formation, our discovery points to a direct link between eviction-coupled erasure of the ubiquitin mark from ubH2B and co-transcriptional pre-mRNA splicing.
-
The U4/U6 Recycling Factor SART3 Has Histone Chaperone Activity and Associates with USP15 to Regulate H2B Deubiquitination
Journal of Biological Chemistry, 2014Co-Authors: Lindsey Long, Joseph P Thelen, Melonnie Furgason, Ashraf Brik, Dongmei Cheng, Mahmood Haj-yahya, Junmin PengAbstract:Post-translational modifications of histone proteins produce dynamic signals that regulate the structure and function of chromatin. Mono-ubiquitination of H2B in the histone tail (at Lys-123 in yeast or Lys-120 in humans) is a conserved modification that has been implicated in the regulation of transcription, replication, and DNA repair processes. In a search for direct effectors of ubH2B, we identified a deubiquitinating enzyme, Usp15, through affinity purification with a nonhydrolyzable ubH2B mimic. In the nucleus, Usp15 indirectly associates with the ubH2B E3 ligase, RNF20/RNF40, and directly associates with a component of the splicing machinery, SART3 (also known as TIP110 or p110). These physical interactions place Usp15 in the vicinity of actively transcribed DNA. Importantly we found that SART3 has previously unrecognized histone chaperone activities. SART3, but not the well-characterized histone chaperone Nap1, enhances Usp15 binding to ubH2B and facilitates Deubiquitination of ubH2B in free histones but not in nucleosomes. These results suggest that SART3 recruits ubH2B, which may be evicted from DNA during transcription, for Deubiquitination by Usp15. In light of the function played by SART3 in U4/U6 di-snRNP formation, our discovery points to a direct link between eviction-coupled erasure of the ubiquitin mark from ubH2B and co-transcriptional pre-mRNA splicing.
Ruaidhri J Carmody - One of the best experts on this subject based on the ideXlab platform.
-
Deubiquitination of nf κb by ubiquitin specific protease 7 promotes transcription
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Amy Colleran, Patricia E Collins, Christine Ocarroll, Abrar Ahmed, Bettina Mcmanus, Patrick A Kiely, Ezra Burstein, Ruaidhri J CarmodyAbstract:NF-κB is the master regulator of the immune response and is responsible for the transcription of hundreds of genes controlling inflammation and immunity. Activation of NF-κB occurs in the cytoplasm through the kinase activity of the IκB kinase complex, which leads to translocation of NF-κB to the nucleus. Once in the nucleus, NF-κB transcriptional activity is regulated by DNA binding-dependent ubiquitin-mediated proteasomal degradation. We have identified the deubiquitinase Ubiquitin Specific Protease-7 (USP7) as a regulator of NF-κB transcriptional activity. USP7 Deubiquitination of NF-κB leads to increased transcription. Loss of USP7 activity results in increased ubiquitination of NF-κB, leading to reduced promoter occupancy and reduced expression of target genes in response to Toll-like– and TNF-receptor activation. These findings reveal a unique mechanism controlling NF-κB activity and demonstrate that the Deubiquitination of NF-κB by USP7 is critical for target gene transcription.
Lindsey Long - One of the best experts on this subject based on the ideXlab platform.
-
the u4 u6 recycling factor sart3 has histone chaperone activity and associates with usp15 to regulate h2b Deubiquitination
Journal of Biological Chemistry, 2014Co-Authors: Lindsey Long, Joseph P Thelen, Melonnie Furgason, Mahmood Hajyahya, Ashraf Brik, Dongmei Cheng, Junmin PengAbstract:Post-translational modifications of histone proteins produce dynamic signals that regulate the structure and function of chromatin. Mono-ubiquitination of H2B in the histone tail (at Lys-123 in yeast or Lys-120 in humans) is a conserved modification that has been implicated in the regulation of transcription, replication, and DNA repair processes. In a search for direct effectors of ubH2B, we identified a deubiquitinating enzyme, Usp15, through affinity purification with a nonhydrolyzable ubH2B mimic. In the nucleus, Usp15 indirectly associates with the ubH2B E3 ligase, RNF20/RNF40, and directly associates with a component of the splicing machinery, SART3 (also known as TIP110 or p110). These physical interactions place Usp15 in the vicinity of actively transcribed DNA. Importantly we found that SART3 has previously unrecognized histone chaperone activities. SART3, but not the well-characterized histone chaperone Nap1, enhances Usp15 binding to ubH2B and facilitates Deubiquitination of ubH2B in free histones but not in nucleosomes. These results suggest that SART3 recruits ubH2B, which may be evicted from DNA during transcription, for Deubiquitination by Usp15. In light of the function played by SART3 in U4/U6 di-snRNP formation, our discovery points to a direct link between eviction-coupled erasure of the ubiquitin mark from ubH2B and co-transcriptional pre-mRNA splicing.
-
The U4/U6 Recycling Factor SART3 Has Histone Chaperone Activity and Associates with USP15 to Regulate H2B Deubiquitination
Journal of Biological Chemistry, 2014Co-Authors: Lindsey Long, Joseph P Thelen, Melonnie Furgason, Ashraf Brik, Dongmei Cheng, Mahmood Haj-yahya, Junmin PengAbstract:Post-translational modifications of histone proteins produce dynamic signals that regulate the structure and function of chromatin. Mono-ubiquitination of H2B in the histone tail (at Lys-123 in yeast or Lys-120 in humans) is a conserved modification that has been implicated in the regulation of transcription, replication, and DNA repair processes. In a search for direct effectors of ubH2B, we identified a deubiquitinating enzyme, Usp15, through affinity purification with a nonhydrolyzable ubH2B mimic. In the nucleus, Usp15 indirectly associates with the ubH2B E3 ligase, RNF20/RNF40, and directly associates with a component of the splicing machinery, SART3 (also known as TIP110 or p110). These physical interactions place Usp15 in the vicinity of actively transcribed DNA. Importantly we found that SART3 has previously unrecognized histone chaperone activities. SART3, but not the well-characterized histone chaperone Nap1, enhances Usp15 binding to ubH2B and facilitates Deubiquitination of ubH2B in free histones but not in nucleosomes. These results suggest that SART3 recruits ubH2B, which may be evicted from DNA during transcription, for Deubiquitination by Usp15. In light of the function played by SART3 in U4/U6 di-snRNP formation, our discovery points to a direct link between eviction-coupled erasure of the ubiquitin mark from ubH2B and co-transcriptional pre-mRNA splicing.
Amy Colleran - One of the best experts on this subject based on the ideXlab platform.
-
Deubiquitination of nf κb by ubiquitin specific protease 7 promotes transcription
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Amy Colleran, Patricia E Collins, Christine Ocarroll, Abrar Ahmed, Bettina Mcmanus, Patrick A Kiely, Ezra Burstein, Ruaidhri J CarmodyAbstract:NF-κB is the master regulator of the immune response and is responsible for the transcription of hundreds of genes controlling inflammation and immunity. Activation of NF-κB occurs in the cytoplasm through the kinase activity of the IκB kinase complex, which leads to translocation of NF-κB to the nucleus. Once in the nucleus, NF-κB transcriptional activity is regulated by DNA binding-dependent ubiquitin-mediated proteasomal degradation. We have identified the deubiquitinase Ubiquitin Specific Protease-7 (USP7) as a regulator of NF-κB transcriptional activity. USP7 Deubiquitination of NF-κB leads to increased transcription. Loss of USP7 activity results in increased ubiquitination of NF-κB, leading to reduced promoter occupancy and reduced expression of target genes in response to Toll-like– and TNF-receptor activation. These findings reveal a unique mechanism controlling NF-κB activity and demonstrate that the Deubiquitination of NF-κB by USP7 is critical for target gene transcription.
Shangda Yang - One of the best experts on this subject based on the ideXlab platform.
-
usp9x mediated Deubiquitination of b cell cll lymphoma 9 potentiates wnt signaling and promotes breast carcinogenesis
Journal of Biological Chemistry, 2019Co-Authors: Zesen Shang, Kai Zhang, Jiao Zhao, Qi Zhang, Shanshan Tian, Na Yu, Shangda YangAbstract:: Hyperactivation of the canonical Wnt-signaling pathway is a prominent feature of a number of human malignancies. Transcriptional activation of this signaling cascade depends on the formation of the β-catenin-B-cell CLL/lymphoma 9 (BCL9)-pygopus (PYGO) family plant homeodomain finger 1 complex, yet how the assembly of this complex is regulated remains to be investigated. Here, using MCF-7, HeLa, HEK293T, MDA-MB-231, and Sf9 cells, along with immunoblotting and immunofluorescence, nano-HPLC-MS/MS, Deubiquitination, immunoprecipitation, and chromatin immunoprecipitation (ChIP) assays, we report that BCL9 physically associates with a protein deubiquitinase, ubiquitin-specific peptidase 9, X-linked (USP9X), and that USP9X removes Lys-63-linked polyubiquitin on Lys-212 of BCL9. Importantly, the USP9X-mediated BCL9 Deubiquitination facilitated the formation of the β-catenin-BCL9-PYGO complex, thereby potentiating the transcriptional activation of Wnt/β-catenin target genes. We also show that USP9X-mediated BCL9 Deubiquitination promotes the proliferation and invasion of breast cancer cells. Together, these results uncover USP9X as a deubiquitinase of BCL9, implicating USP9X in Wnt/β-catenin signaling and breast carcinogenesis.
-
USP9X-mediated Deubiquitination of B-cell CLL/lymphoma 9 potentiates Wnt signaling and promotes breast carcinogenesis
Journal of Biological Chemistry, 2019Co-Authors: Zesen Shang, Kai Zhang, Jiao Zhao, Qi Zhang, Shanshan Tian, Na Yu, Shangda YangAbstract:Hyperactivation of the canonical Wnt-signaling pathway is a prominent feature of a number of human malignancies. Transcriptional activation of this signaling cascade depends on the formation of the β-catenin-B-cell CLL/lymphoma 9 (BCL9)-pygopus (PYGO) family plant homeodomain finger 1 complex, yet how the assembly of this complex is regulated remains to be investigated. Here, using MCF-7, HeLa, HEK293T, MDA-MB-231, and Sf9 cells, along with immunoblotting and immunofluorescence, nano-HPLC-MS/MS, Deubiquitination, immunoprecipitation, and chromatin immunoprecipitation (ChIP) assays, we report that BCL9 physically associates with a protein deubiquitinase, ubiquitin-specific peptidase 9, X-linked (USP9X), and that USP9X removes Lys-63-linked polyubiquitin on Lys-212 of BCL9. Importantly, the USP9X-mediated BCL9 Deubiquitination facilitated the formation of the β-catenin-BCL9-PYGO complex, thereby potentiating the transcriptional activation of Wnt/β-catenin target genes. We also show that USP9X-mediated BCL9 Deubiquitination promotes the proliferation and invasion of breast cancer cells. Together, these results uncover USP9X as a deubiquitinase of BCL9, implicating USP9X in Wnt/β-catenin signaling and breast carcinogenesis.