SPIB

更新于：2025-01-23

基本信息

别名

SPI-B、Spi-B transcription factor、SPIB

+ [1]

简介

Sequence specific transcriptional activator which binds to the PU-box, a purine-rich DNA sequence (5'-GAGGAA-3') that can act as a lymphoid-specific enhancer. Promotes development of plasmacytoid dendritic cells (pDCs), also known as type 2 DC precursors (pre-DC2) or natural interferon (IFN)-producing cells. These cells have the capacity to produce large amounts of interferon and block viral replication. May be required for B-cell receptor (BCR) signaling, which is necessary for normal B-cell development and antigenic stimulation.

关联

100 项与 SPIB 相关的临床结果

登录后查看更多信息

100 项与 SPIB 相关的转化医学

登录后查看更多信息

0 项与 SPIB 相关的专利（医药）

登录后查看更多信息

363

项与 SPIB 相关的文献（医药）

2024-12-16·Cancer Research

Selective Enhancer Gain-of-Function Deregulates MYC Expression in Multiple Myeloma

Article

作者: Kodgule, Rohan ; Clement, Kendell ; Heilpern-Mallory, Daniel ; Rahmat, Mahshid ; Alberge, Jean-Baptiste ; Pinello, Luca ; Ryan, Russell J.H. ; Engreitz, Jesse M. ; Getz, Gad ; Fulco, Charles P. ; Sklavenitis-Pistofidis, Romanos ; Nilsson, Katarina ; Dorfman, David ; Ghobrial, Irene M.

AbstractMYC deregulation occurs in the majority of multiple myeloma cases and is associated with progression and worse prognosis. Enhanced MYC expression occurs in about 70% of patients with multiple myeloma, but it is known to be driven by translocation or amplification events in only ∼40% of myelomas. Here, we used CRISPR interference to uncover an epigenetic mechanism of MYC regulation whereby increased accessibility of a plasma cell-type–specific enhancer leads to increased MYC expression. This native enhancer activity was not associated with enhancer hijacking events but led to specific binding of cMAF, IRF4, and SPIB transcription factors that activated MYC expression in the absence of known genetic aberrations. In addition, focal amplification was another mechanism of activation of this enhancer in approximately 3.4% of patients with multiple myeloma. Together, these findings define an epigenetic mechanism of MYC deregulation in multiple myeloma beyond known translocations or amplifications and point to the importance of noncoding regulatory elements and their associated transcription factor networks as drivers of multiple myeloma progression.Significance: The discovery of a native developmental enhancer that sustains the expression of MYC in a subset of myelomas could help identify predictive biomarkers and therapeutic targets to improve the outcomes of patients with multiple myeloma.

2024-12-01·Immunology Letters

Intestinal epithelial vitamin D receptor defense against inflammatory bowel disease via regulating microfold cells

Article

作者: Chen, Xin ; Chen, Yunzi ; Wu, Yuxuan ; Sun, Xiaomeng ; Zhang, Na ; Han, Chenhua

Vitamin D receptor (VDR) is involved in the pathogenesis of inflammatory bowel disease (IBD). However, the mechanism of VDR in IBD is still unclear. Microfold cells (M cells) mediated antigen-sampling pathway is central in developing immune responses to pathogenic and commensal bacteria and related to IBD. We found that Intestinal epithelial cell-specific knockdown of VDR(VDR^IEC-KO) increases the susceptibility of mice to experimental colitis induced by sodium dextran sulfate(DSS) by producing more M cells. Knockdown VDR in intestinal epithelial cells increased RANKL-induced microfold cells and promoted the ability of microfold cells to uptake S. Typhimurium (S. T.). Mechanistically, we demonstrated that knockdown VDR promoted the differentiation and maturation of M cells via the Spi-B-dependent pathway. We conclude that M cells may be a potential target of VDR for treating intestinal mucosal barrier dysfunction in IBD.

2024-11-01·International Journal of Biological Macromolecules

circE2F1-encoded peptide inhibits circadian machinery essential for nucleotide biosynthesis and tumor progression via repressing SPIB/E2F1 axis

Article

作者: Yang, Chunhui ; Li, Qilan ; Wang, Jianqun ; Tong, Qiangsong ; Du, Xinyi ; Tian, Minxiu ; Du, Xinyu ; Zheng, Liduan ; Cheng, Yang ; Wang, Xiaojing ; Li, Dan

Circadian clock dominates a variety of biological activities, while its roles and regulatory mechanisms in neuroblastoma (NB), a pediatric extracranial malignancy, still remain largely elusive. Herein, through comprehensive analyses of public datasets, E2F transcription factor 1 (E2F1) and its circular RNA (circE2F1)-encoded 99-amino acid peptide (E2F1-99aa) were identified as vital regulators of circadian machinery essential for purine and pyrimidine biosynthesis during NB progression. Mechanistically, through interaction with Spi-B transcription factor (SPIB), E2F1 was transactivated to up-regulate circadian machinery genes (CRY1 and TIMELESS), resulting in relief of CLOCK/BMAL1-repressed transcription of enzymes (DHODH, PAICS, or PPAT) essential for de novo purine and pyrimidine biosynthesis. The biogenesis of circE2F1 was repressed by eukaryotic translation initiation factor 4A3 (EIF4A3), while E2F1-99aa or its truncated peptide competitively bound to SPIB, leading to decrease in SPIB-E2F1 interaction, circadian machinery and nucleotide biosynthetic gene expression, purine or pyrimidine biosynthesis, tumorigenesis, and aggresiveness of NB cells. In clinical NB cases, high EIF4A3, E2F1 or SPIB expression was correlated with low survival possibility of patients, while lower circE2F1 or E2F1-99aa levels were associated with advanced stages and tumor progression. These results indicate that circE2F1-encoded peptide inhibits circadian machinery essential for nucleotide biosynthesis and tumor progression via repressing SPIB/E2F1 axis.

项与 SPIB 相关的新闻（医药）

2023-04-26

·生物谷

Cell Death Differ.：科学家们揭示了TFAP4在淋巴肿瘤发生中的机制

癌基因c-MYC在约70%的人类癌症中异常高表达，如伯基特淋巴瘤（BL）。癌基因c-MYC在约70%的人类癌症中异常高表达，如伯基特淋巴瘤（BL）。由于BL和其他淋巴系统恶性肿瘤的发展需要额外的遗传或表观遗传学畸变，这些畸变与失调的c-MYC表达协同作用，研究者之前在体内进行无偏见的全基因组功能性遗传筛选，确定转录因子TFAP4（也称为AP-4）是最热门的基因之一。 TFAP4是一种碱性螺旋-环-螺旋-亮氨酸拉链转录因子，Tfap4的表达本身受到c-MYC的直接调控。TFAP4通过与c-MYC的功能相互作用，包括与相同的基因启动子元件的结合，有助于几种c-MYC调节的细胞过程。值得注意的是，TFAP4通过结合和调节相同的基因启动子，在感染性攻击后维持生发中心B细胞中c-MYC驱动的增殖和成熟信号至关重要。因此，TFAP4是一种重要的转录因子，作用于c-MYC的下游和/或与c-MYC平行，调节成熟B淋巴细胞的增殖和Ig类转换。图片来源：https://doi.org/10.1038/s41418-023-01145-w 近日，来自沃尔特和伊丽莎.霍尔医学研究所的研究者们在Cell Death Differ.杂志上发表了题为“Deletion of the transcriptional regulator TFAP4 accelerates c-MYC-driven lymphomagenesis”的文章，该研究发现TFAP4的缺失导致B细胞早期发育过程中分化受阻，从而加速c-MYC驱动的淋巴瘤发展。许多淋巴系统恶性肿瘤是由c-MYC表达失调与其他遗传病变共同作用引起的。虽然已经发现了许多这种协同遗传病变，并对其功能进行了表征，但主要患者样本的DNA序列数据表明，还存在更多的协同遗传病变。然而，他们对c-MYC驱动的淋巴瘤的贡献的性质尚未得到研究。在先前的全基因组CRISPR敲除体内原代细胞筛选中，研究者确定TFAP4是c-MYC驱动的淋巴瘤发展的有效抑制剂。Eµ-MYC转基因造血干细胞和祖细胞（HSPCs）中TFAP4的CRISPR缺失，以及将这些操纵的HSPCs移植到致命辐照的动物中，显著加速了cMYC驱动的淋巴瘤的发展。有趣的是，TFAP4缺陷型Eµ-MYC淋巴瘤都发生在B细胞发育的前B细胞阶段。这一观察结果促使研究者对移植有Eµ-MYC/Cas9 HSPCs的白血病前期小鼠的前B细胞的转录谱进行表征，这些HSPCs已用靶向TFAP4的sgRNA转导。该分析显示，TFAP4缺失降低了B细胞分化的几种主要调节因子的表达，如Spi1、SpiB和Pax5，它们是TFAP4和MYC的直接靶基因。 Tfap4的缺失加速了c-MYC驱动的淋巴结肿瘤图片来源：https://doi.org/10.1038/s41418-023-01145-w 综上所述，在c-MYC驱动的血癌中恢复TFAP4的表达，可能不是通过杀死肿瘤细胞，而是通过诱导自我更新的前B淋巴瘤细胞库正常分化为增殖性较低的未成熟/成熟B细胞来改善疾病进展，尽管前提是这些细胞依赖于TFAP4持续缺失来维持淋巴瘤，而不仅仅是淋巴瘤的发展。（生物谷 Bioon.com）参考文献 Margaret A. Potts et al. Deletion of the transcriptional regulator TFAP4 accelerates c-MYC-driven lymphomagenesis. Cell Death Differ. 2023 Mar 9. doi: 10.1038/s41418-023-01145-w.

AACR会议临床结果临床1期

分析

对领域进行一次全面的分析。

或

查看完整样例数据

来和芽仔聊天吧

立即开始免费试用!

智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。

立即开始数据试用!

智慧芽新药库数据也通过智慧芽数据服务平台，以API或者数据包形式对外开放，助您更加充分利用智慧芽新药情报信息。