人类癌症中蛋白质自身抑制的广泛改变
Jorge A Holguin-Cruz1, Jennifer M Bui1, Ashwani Jha1
1Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Cell systems
|February 17, 2024
概括
癌细胞利用蛋白质自身抑制开关中的遗传变化. 这些变化,特别是在抑制性全开关 (IASs) 中,驱动癌症的进展,并确定新的癌症驱动因素.
科学领域:
- 分子生物学分子生物学
- 癌症基因组学 癌症基因组学
- 生物物理学的生物物理.
背景情况:
- 自抑制是信号蛋白的关键调节机制.
- 减少自身抑制与癌症有关,但其一般作用尚不清楚.
研究的目的:
- 为了调查自身抑制是否在癌症中被广泛改变.
- 通过抑制性全开关 (IASs) 中的突变来识别癌症驱动因素.
主要方法:
- 在不同癌症类型中分析与癌症相关的突变 (误解,indels,融合).
- 经常变化的IAS的识别.
- 对PPP3CA (氨酸) 突变的生物分子模拟.
- 转录组分析.
主要成果:
- 癌症突变在所有癌症类型的IAS中都具有丰富性.
- 经常发生的IAS突变可以识别已知的和新的癌症驱动因素.
- 在PPP3CA的IAS中发生的突变改变了自身抑制,增加了calcineurin信号,并影响了转录组.
结论:
- 影响蛋白质自身抑制的遗传变化在癌症中被积极选择.
- IAS是关键的监管要素,经常针对癌症的发展.
相关概念视频
mTOR Signaling and Cancer Progression
3.8K
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...
3.8K
Loss of Tumor Suppressor Gene Functions
4.8K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.8K
Abnormal Proliferation
4.5K
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...
4.5K
Inhibition of Cdk Activity
4.8K
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...
4.8K
The Intrinsic Apoptotic Pathway
6.5K
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...
6.5K
Adaptive Mechanisms in Cancer Cells
5.8K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.8K


