CBP和p300介导的JAK/STAT与Ras/AP-1信号通路的核内整合
Nuclear integration of JAK/STAT and Ras/AP-1 signaling by CBP and p300.
作者信息
Horvai A E, Xu L, Korzus E, Brard G, Kalafus D, Mullen T M, Rose D W, Rosenfeld M G, Glass C K
机构信息
Division of Endocrinology and Metabolism, University of California at San Diego, La Jolla 92093-0651, USA.
出版信息
Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1074-9. doi: 10.1073/pnas.94.4.1074.
Abstract
We report that interferon gamma (IFN-gamma) inhibits transcription of the macrophage scavenger receptor gene by antagonizing the Ras-dependent activities of AP-1 and cooperating ets domain transcription factors, apparently as a result of competition between AP-1/ets factors and activated STAT1 for limiting amounts of CBP and p300. Consistent with this model, STAT1 alpha interacts directly with CBP in cells, and microinjection of anti-CBP and anti-p300 antibodies blocks transcriptional responses to IFN-gamma. Cells lacking STAT1 fail to inhibit AP-1/ets activity, and overexpression of CBP both potentiates IFN-gamma-dependent transcription and relieves AP-1/ets repression. Thus, CBP and p300 integrate both positive and negative effects of IFN-gamma on gene expression by serving as essential coactivators of STAT1 alpha, modulating gene-specific responses to simultaneous activation of two or more signal transduction pathways.
摘要
我们报告，干扰素γ（IFN-γ）通过拮抗AP-1的Ras依赖性活性和协同ets结构域转录因子来抑制巨噬细胞清道夫受体基因的转录，这显然是由于AP-1/ets因子与活化的STAT1之间竞争有限量的CBP和p300所致。与该模型一致，STAT1α在细胞中直接与CBP相互作用，显微注射抗CBP和抗p300抗体可阻断对IFN-γ的转录反应。缺乏STAT1的细胞无法抑制AP-1/ets活性，CBP的过表达既增强了IFN-γ依赖性转录，又减轻了AP-1/ets的抑制作用。因此，CBP和p300通过作为STAT1α的必需共激活因子，整合IFN-γ对基因表达的正负效应，调节对两个或更多信号转导途径同时激活的基因特异性反应。
相似文献
1
Nuclear integration of JAK/STAT and Ras/AP-1 signaling by CBP and p300.CBP和p300介导的JAK/STAT与Ras/AP-1信号通路的核内整合
Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1074-9. doi: 10.1073/pnas.94.4.1074.
2
Two contact regions between Stat1 and CBP/p300 in interferon gamma signaling.干扰素γ信号通路中Stat1与CBP/p300之间的两个接触区域。
Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15092-6. doi: 10.1073/pnas.93.26.15092.
3
Ras/mitogen-activated protein kinase signaling activates Ets-1 and Ets-2 by CBP/p300 recruitment.Ras/丝裂原活化蛋白激酶信号通过募集CBP/p300激活Ets-1和Ets-2。
Mol Cell Biol. 2004 Dec;24(24):10954-64. doi: 10.1128/MCB.24.24.10954-10964.2004.
4
Peroxisome proliferator-activated receptor gamma-dependent repression of the inducible nitric oxide synthase gene.过氧化物酶体增殖物激活受体γ对诱导型一氧化氮合酶基因的依赖性抑制作用
Mol Cell Biol. 2000 Jul;20(13):4699-707. doi: 10.1128/MCB.20.13.4699-4707.2000.
5
6
Overexpression and ribozyme-mediated targeting of transcriptional coactivators CREB-binding protein and p300 revealed their indispensable roles in adipocyte differentiation through the regulation of peroxisome proliferator-activated receptor gamma.转录共激活因子CREB结合蛋白和p300的过表达及核酶介导的靶向作用揭示了它们通过调节过氧化物酶体增殖物激活受体γ在脂肪细胞分化中发挥不可或缺的作用。
J Biol Chem. 2002 May 10;277(19):16906-12. doi: 10.1074/jbc.M200585200. Epub 2002 Mar 7.
7
The transcriptional coactivator CREB-binding protein cooperates with STAT1 and NF-kappa B for synergistic transcriptional activation of the CXC ligand 9/monokine induced by interferon-gamma gene.转录共激活因子CREB结合蛋白与STAT1和核因子κB协同作用，对CXC配体9/γ干扰素诱导的单核因子基因进行转录激活。
J Biol Chem. 2003 Jan 3;278(1):651-60. doi: 10.1074/jbc.M204544200. Epub 2002 Oct 25.
8
Transcription factor-specific requirements for coactivators and their acetyltransferase functions.转录因子对共激活因子及其乙酰转移酶功能的特异性需求。
Science. 1998 Jan 30;279(5351):703-7. doi: 10.1126/science.279.5351.703.
9
Mycobacterium tuberculosis inhibits IFN-gamma transcriptional responses without inhibiting activation of STAT1.结核分枝杆菌抑制IFN-γ转录反应，但不抑制STAT1的激活。
J Immunol. 1999 Oct 1;163(7):3898-906.
10
Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300/CREB-binding protein (CBP).由共激活因子p300/CREB结合蛋白（CBP）调控的活化T细胞核因子（NFAT）依赖性反式激活。
J Exp Med. 1998 Jun 15;187(12):2031-6. doi: 10.1084/jem.187.12.2031.
引用本文的文献
1
Paradoxical cancer cell proliferation after FGFR inhibition through decreased p21 signaling in FGFR1-amplified breast cancer cells.成纤维细胞生长因子受体（FGFR）抑制后，FGFR1 扩增型乳腺癌细胞中 p21 信号通路减少导致的癌性细胞增殖悖论。
Breast Cancer Res. 2024 Mar 29;26(1):54. doi: 10.1186/s13058-024-01808-7.
2
Preclinical and clinical evaluation of the Janus Kinase inhibitor ruxolitinib in multiple myeloma.Janus 激酶抑制剂芦可替尼在多发性骨髓瘤的临床前和临床评估。
Oncotarget. 2024 Feb 5;15:65-75. doi: 10.18632/oncotarget.28547.
3
The complementary roles of STAT3 and STAT1 in cancer biology: insights into tumor pathogenesis and therapeutic strategies.STAT3 和 STAT1 在癌症生物学中的互补作用：对肿瘤发病机制和治疗策略的深入了解。
Front Immunol. 2023 Nov 8;14:1265818. doi: 10.3389/fimmu.2023.1265818. eCollection 2023.
4
SIAH ubiquitin E3 ligases as modulators of inflammatory gene expression.SIAH泛素E3连接酶作为炎症基因表达的调节因子。
Heliyon. 2022 Mar 1;8(3):e09029. doi: 10.1016/j.heliyon.2022.e09029. eCollection 2022 Mar.
5
The JAK/STAT signaling pathway: from bench to clinic.JAK/STAT 信号通路：从基础到临床。
Signal Transduct Target Ther. 2021 Nov 26;6(1):402. doi: 10.1038/s41392-021-00791-1.
6
CD40 Cross-Linking Induces Migration of Renal Tumor Cell through Nuclear Factor of Activated T Cells (NFAT) Activation.CD40 交联通过激活 T 细胞核因子（NFAT）诱导肾肿瘤细胞迁移。
Int J Mol Sci. 2021 Aug 18;22(16):8871. doi: 10.3390/ijms22168871.
7
p300 Serine 89: A Critical Signaling Integrator and Its Effects on Intestinal Homeostasis and Repair.p300丝氨酸89：一种关键的信号整合因子及其对肠道稳态和修复的影响。
Cancers (Basel). 2021 Mar 14;13(6):1288. doi: 10.3390/cancers13061288.
8
Injectable hydrogel with MSNs/microRNA-21-5p delivery enables both immunomodification and enhanced angiogenesis for myocardial infarction therapy in pigs.载有 MSNs/miRNA-21-5p 的可注射水凝胶通过免疫调节和增强血管生成实现猪心肌梗死的治疗。
Sci Adv. 2021 Feb 24;7(9). doi: 10.1126/sciadv.abd6740. Print 2021 Feb.
9
PHLPP1 counter-regulates STAT1-mediated inflammatory signaling.PHLPP1 拮抗 STAT1 介导的炎症信号通路。
Elife. 2019 Aug 13;8:e48609. doi: 10.7554/eLife.48609.
10
LPS promotes HBO1 stability via USP25 to modulate inflammatory gene transcription in THP-1 cells.脂多糖通过 USP25 促进 HBO1 稳定性，从而调节 THP-1 细胞中的炎症基因转录。
Biochim Biophys Acta Gene Regul Mech. 2018 Sep;1861(9):773-782. doi: 10.1016/j.bbagrm.2018.08.001. Epub 2018 Aug 4.
本文引用的文献
1
Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation.p300/CBP与bHLH蛋白在肌肉和B细胞分化中的相互作用及功能协作。
Genes Dev. 1996 Oct 1;10(19):2478-90. doi: 10.1101/gad.10.19.2478.
2
Transient expression of translation initiation factor eIF-4C during the 2-cell stage of the preimplantation mouse embryo: identification by mRNA differential display and the role of DNA replication in zygotic gene activation.翻译起始因子eIF-4C在植入前小鼠胚胎2细胞期的瞬时表达：通过mRNA差异显示鉴定及DNA复制在合子基因激活中的作用
Dev Biol. 1996 Mar 15;174(2):190-201. doi: 10.1006/dbio.1996.0065.
3
A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors.一种CBP整合蛋白复合体介导核受体的转录激活和AP-1抑制作用。
Cell. 1996 May 3;85(3):403-14. doi: 10.1016/s0092-8674(00)81118-6.
4
CBP as a transcriptional coactivator of c-Myb.CBP作为c-Myb的转录共激活因子。
Genes Dev. 1996 Mar 1;10(5):528-40. doi: 10.1101/gad.10.5.528.
5
Regulation of cytokine-inducible nitric oxide synthase in cardiac myocytes and microvascular endothelial cells. Role of extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2) and STAT1 alpha.心肌细胞和微血管内皮细胞中细胞因子诱导型一氧化氮合酶的调控。细胞外信号调节激酶1和2（ERK1/ERK2）及信号转导和转录激活因子1α（STAT1α）的作用。
J Biol Chem. 1996 Jan 12;271(2):1111-7. doi: 10.1074/jbc.271.2.1111.
6
Interferon gamma-induced transcription of the high-affinity Fc receptor for IgG requires assembly of a complex that includes the 91-kDa subunit of transcription factor ISGF3.γ干扰素诱导的IgG高亲和力Fc受体转录需要一种复合物的组装，该复合物包括转录因子ISGF3的91-kDa亚基。
Proc Natl Acad Sci U S A. 1993 May 1;90(9):4314-8. doi: 10.1073/pnas.90.9.4314.
7
Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor.抗小鼠清道夫受体单克隆抗体抑制二价阳离子非依赖性巨噬细胞黏附
Nature. 1993 Jul 22;364(6435):343-6. doi: 10.1038/364343a0.
8
The genomic structure of the murine ICSBP gene reveals the presence of the gamma interferon-responsive element, to which an ISGF3 alpha subunit (or similar) molecule binds.小鼠ICSBP基因的基因组结构显示存在γ干扰素反应元件，一种ISGF3α亚基（或类似物）分子可与之结合。
Mol Cell Biol. 1993 Jul;13(7):3951-63. doi: 10.1128/mcb.13.7.3951-3963.1993.
9
Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain.一种结合并增强c-Jun激活结构域的癌蛋白和紫外线反应性蛋白激酶的鉴定。
Genes Dev. 1993 Nov;7(11):2135-48. doi: 10.1101/gad.7.11.2135.
10
Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins.Jak-STAT信号通路以及对干扰素和其他细胞外信号蛋白的转录激活。
Science. 1994 Jun 3;264(5164):1415-21. doi: 10.1126/science.8197455.
Zotero 插件