ジャーナル: Nat Commun / 年: 2025 タイトル: DSS1 is required for proper Integrator-PP2A function. 著者: Congling Xu / Qian-Xing Zhou / Hai Zheng / Aixia Song / Wen-Ying Zhao / Ting-Ting Xu / Yan Xiong / Yi-Jie Zhang / Zixuan Huang / Yanhui Xu / Jingdong Cheng / Fei Xavier Chen / 要旨: Integrator-PP2A (INTAC) is a highly modular complex orchestrating the transition of paused RNA polymerase II into productive elongation or promoter-proximal premature termination, with its loss ...Integrator-PP2A (INTAC) is a highly modular complex orchestrating the transition of paused RNA polymerase II into productive elongation or promoter-proximal premature termination, with its loss resulting in transcription dysregulation and genome instability. Here, we identify human DSS1-a flexible 70-residue protein found in multiple functionally diverse complexes including the 26S proteasome-as an integral subunit of the INTAC backbone. Structural analysis of DSS1-INTAC, both alone and in association with paused polymerase, demonstrates intimate interactions between DSS1 and the INTAC backbone. We identify tryptophan 39 of DSS1 as being critical for interacting with INTAC and find that its mutation disrupts DSS1's interaction with INTAC, while maintaining DSS1's interaction with the proteasome. This substitution not only impairs INTAC-dependent transcriptional regulation, but also reveals that INTAC is DSS1's major chromatin-bound form. Together, our findings reveal a role for DSS1 in supporting the structure and regulatory functions of INTAC.
Integratorcomplexsubunit9 / Int9 / Protein related to CPSF subunits of 74 kDa / RC-74
分子量: 73891.219 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: INTS9, RC74 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q9NV88
#3: タンパク質
Integratorcomplexsubunit11 / Int11 / Cleavage and polyadenylation-specific factor 3-like protein / CPSF3-like protein / Protein ...Int11 / Cleavage and polyadenylation-specific factor 3-like protein / CPSF3-like protein / Protein related to CPSF subunits of 68 kDa / RC-68
DNA-directedRNApolymeraseIIsubunitRPB3 / RNA polymerase II subunit 3 / RNA polymerase II subunit B3 / DNA-directed RNA polymerase II 33 kDa ...RNA polymerase II subunit 3 / RNA polymerase II subunit B3 / DNA-directed RNA polymerase II 33 kDa polypeptide / RPB33 / DNA-directed RNA polymerase II subunit C / RPB31
分子量: 31439.074 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: POLR2C, A-152E5.7 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P19387
#18: タンパク質
DNA-directedRNApolymeraseIIsubunitRPB9 / RNA polymerase II subunit B9 / DNA-directed RNA polymerase II subunit I / RNA polymerase II 14.5 ...RNA polymerase II subunit B9 / DNA-directed RNA polymerase II subunit I / RNA polymerase II 14.5 kDa subunit / RPB14.5
分子量: 14541.221 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: POLR2I / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P36954
#20: タンパク質
DNA-directedRNApolymeraseIIsubunitRPB11-a / RNA polymerase II subunit B11-a / RPB11a / DNA-directed RNA polymerase II subunit J-1 / RNA ...RNA polymerase II subunit B11-a / RPB11a / DNA-directed RNA polymerase II subunit J-1 / RNA polymerase II 13.3 kDa subunit
分子量: 13310.284 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: POLR2J, POLR2J1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P52435
#30: タンパク質
DNA-directedRNApolymeraseIIsubunitRPB7 / RNA polymerase II subunit B7 / DNA-directed RNA polymerase II subunit G / RNA polymerase II 19 kDa ...RNA polymerase II subunit B7 / DNA-directed RNA polymerase II subunit G / RNA polymerase II 19 kDa subunit / RPB19
分子量: 19314.283 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: POLR2G, RPB7 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P62487
#31: タンパク質
DNA-directedRNApolymeraseIIsubunitRPB4 / RNA polymerase II subunit B4 / DNA-directed RNA polymerase II subunit D / RNA polymerase II 16 kDa ...RNA polymerase II subunit B4 / DNA-directed RNA polymerase II subunit D / RNA polymerase II 16 kDa subunit / RPB16
分子量: 16331.255 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: POLR2D / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: O15514
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タンパク質・ペプチド , 4種, 4分子 nMpo
#9: タンパク質・ペプチド
THR-SER-PRO-SER-TYR-SER-PRO-THR
分子量: 838.860 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト)
#36: タンパク質・ペプチド
Unknown2
分子量: 1464.797 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト)
#37: タンパク質・ペプチド
SER-PRO-THR-SER
分子量: 390.389 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト)
#38: タンパク質・ペプチド
SER-PRO-LYS-TYR-SER-PRO-THR-SER
分子量: 866.936 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト)
Serine/threonine-proteinphosphatase2A65kDaregulatorysubunitAalphaisoform / PP2Aa / Medium tumor antigen-associated 61 kDa protein / PP2A subunit A isoform PR65-alpha / PP2A ...PP2Aa / Medium tumor antigen-associated 61 kDa protein / PP2A subunit A isoform PR65-alpha / PP2A subunit A isoform R1-alpha
分子量: 65378.344 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PPP2R1A / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P30153
#11: タンパク質
Serine/threonine-proteinphosphatase2Acatalyticsubunitalphaisoform / PP2A-alpha / Replication protein C / RP-C
分子量: 35636.152 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PPP2CA / 発現宿主: Homo sapiens (ヒト) 参照: UniProt: P67775, protein-serine/threonine phosphatase
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DNA-directed RNA polymerases I, II, and III subunit ... , 5種, 5分子 4568a
#15: タンパク質
DNA-directedRNApolymerasesI, II, andIIIsubunitRPABC1 / RNA polymerases I / II / and III subunit ABC1 / DNA-directed RNA polymerase II 23 kDa polypeptide / ...RNA polymerases I / II / and III subunit ABC1 / DNA-directed RNA polymerase II 23 kDa polypeptide / DNA-directed RNA polymerase II subunit E / RPB5 homolog / XAP4
分子量: 24644.318 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: POLR2E / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P19388
#16: タンパク質
DNA-directedRNApolymerasesI, II, andIIIsubunitRPABC2 / RNA polymerases I / II / and III subunit ABC2 / DNA-directed RNA polymerase II subunit F / DNA- ...RNA polymerases I / II / and III subunit ABC2 / DNA-directed RNA polymerase II subunit F / DNA-directed RNA polymerases I / and III 14.4 kDa polypeptide / RPABC14.4 / RPB14.4 / RPB6 homolog / RPC15
分子量: 14477.001 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: POLR2F, POLRF / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P61218
#17: タンパク質
DNA-directedRNApolymerasesI, II, andIIIsubunitRPABC3 / RNA polymerases I / II / and III subunit ABC3 / DNA-directed RNA polymerase II subunit H / DNA- ...RNA polymerases I / II / and III subunit ABC3 / DNA-directed RNA polymerase II subunit H / DNA-directed RNA polymerases I / and III 17.1 kDa polypeptide / RPB17 / RPB8 homolog / hRPB8
分子量: 17162.273 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: POLR2H / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P52434
#19: タンパク質
DNA-directedRNApolymerasesI, II, andIIIsubunitRPABC5 / RNA polymerases I / II / and III subunit ABC5 / DNA-directed RNA polymerase III subunit L / RNA ...RNA polymerases I / II / and III subunit ABC5 / DNA-directed RNA polymerase III subunit L / RNA polymerase II 7.6 kDa subunit / RPB7.6 / RPB10 homolog
分子量: 7655.123 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: POLR2L / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P62875
#21: タンパク質
DNA-directedRNApolymerasesI, II, andIIIsubunitRPABC4 / RNA polymerases I / II / and III subunit ABC4 / ABC10-alpha / DNA-directed RNA polymerase II ...RNA polymerases I / II / and III subunit ABC4 / ABC10-alpha / DNA-directed RNA polymerase II subunit K / RNA polymerase II 7.0 kDa subunit / RPB7.0 / RPB10alpha
分子量: 7018.244 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: POLR2K / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P53803
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DNA鎖 , 2種, 2分子 bd
#22: DNA鎖
DNA (48-MER)
分子量: 14932.533 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト)
#23: DNA鎖
DNA (45-MER)
分子量: 13694.721 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト)
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Negative elongation factor ... , 4種, 4分子 efgh
#24: タンパク質
NegativeelongationfactorA / NELF-A / Wolf-Hirschhorn syndrome candidate 2 protein
分子量: 57343.598 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: NELFA, WHSC2, P/OKcl.15 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q9H3P2
#25: タンパク質
NegativeelongationfactorB / NELF-B / Cofactor of BRCA1
分子量: 65779.227 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: NELFB, COBRA1, KIAA1182 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q8WX92
#26: タンパク質
NegativeelongationfactorC/D / NELF-C/D / TH1-like protein