抑制CDK9通过病毒模拟激活先天免疫反应
Shivani Yalala1, Aishwarya Gondane1, Ninu Poulose2
1Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
概括
抑制CDK9会触发癌细胞的先天性免疫反应,从而导致RNA错误拼接,模仿病毒感染. 这种机制导致癌细胞死亡,并可能增强前列腺癌的免疫治疗.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 癌细胞往往表现出高转录率,使它们易受转录激酶 (CDK9) 等转录激酶的药物影响.
- CDK9抑制剂对癌细胞增殖的影响背后的精确机制尚未完全理解.
研究的目的:
- 阐明CDK9抑制诱导的癌细胞选择性抗增殖作用的机制.
- 为了研究先天免疫反应激活在CDK9抑制中的作用.
- 探索CDK9抑制剂在治疗前列腺癌中的潜力.
主要方法:
- 利用MYC过度表达前列腺癌细胞.
- 采用时间解析的转录概况 (SLAM-seq),向蛋白质组学和ChIP-seq.
- 评估了dsRNA激活激酶活性和NFκB信号通路.
主要成果:
- 抑制CDK9导致错误拼接RNA的积累,激活dSRNA激活酶.
- 癌细胞表现出病毒模仿性,具有抑制的全球转录,但有选择性的细胞因子生产.
- 由NFκB驱动的细胞因子信号被转录和在秘密层面上激活.
- CDK9抑制在体外诱导了DNA损伤,并确定了具有高基因组不稳定的前列腺癌.
结论:
- 抑制CDK9通过癌细胞中的病毒模拟激活先天免疫力.
- 这一途径对于CDK9抑制剂的抗增殖作用至关重要.
- 抑制CDK9显示了增强前列腺癌免疫疗法的潜力.
相关概念视频
Immune Response Against Viral Pathogens
777
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
777
Inhibition of Cdk Activity
4.7K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K
Cytotoxic T Cells-mediated Immune Response
903
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
903
Cells of the Innate Immune Response
1.6K
The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
1.6K
Positive Regulator Molecules
5.4K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.4K
S-Cdk Initiates DNA Replication
4.7K
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.7K


