在人类恶性瘤中,CIP2A抑制了PP2A
Melissa R Junttila1, Pietri Puustinen, Minna Niemelä
1Centre for Biotechnology, University of Turku and Abo Akademi University, 20520 Turku, Finland.
Cell
|July 17, 2007
概括
癌症抑制剂PP2A (CIP2A) 是一种新发现的瘤蛋白,可以抑制蛋白酸酶2A (PP2A) 的活性. CIP2A稳定了瘤转录因子c-Myc,促进了人类癌症的发展.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 蛋白酸酶2A (PP2A) 抑制对人类细胞转化至关重要.
- 人类癌症中PP2A抑制的分子机制在很大程度上是未知的.
研究的目的:
- 为了识别和描述具有致癌活性的PP2A细胞抑制剂.
- 阐明这种抑制剂在人类恶性瘤中的作用.
主要方法:
- 蛋白相互作用研究以确定CIP2A.
- 酶活性测定用于测量PP2A抑制.
- 细胞对转化和瘤形成的测试.
- 对人类癌症中CIP2A表达的分析.
主要成果:
- 一种新型蛋白质,PP2A的癌症抑制剂 (CIP2A),被确定为PP2A抑制剂.
- CIP2A与c-Myc直接相互作用,抑制了PP2A在素62 (S62) 的活性.
- CIP2A 防止c-Myc 降解,促进 anchorage 独立生长,并诱导瘤形成.
- 在头部和部状细胞癌 (HNSCC) 和结肠癌中,CIP2A过度表达.
结论:
- CIP2A是一种抑制PP2A和稳定c-Myc的人类瘤蛋白.
- CIP2A在人类恶性瘤的发展中发挥着重要作用.
相关概念视频
Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Inhibition of Cdk Activity
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...
Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Inhibition of CDK Activity
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...


