在K54的TAZ的Sirtuin5介导脱乙化促进了黑色素瘤的发展
Garam Kim1, Poshan Yugal Bhattarai1, Sung-Chul Lim2
1College of Pharmacy, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju, 501-759, Republic of Korea.
Cellular oncology (Dordrecht, Netherlands)
|December 19, 2023
概括
TAZ中的一种新型乙化开关,由SIRT5调节,控制其在黑色素瘤中的核定位. 这种SIRT5/TAZ通路对于CTGF表达和转移性黑色素瘤的进展至关重要.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- YAP/TAZ的核积累是各种癌症 (包括黑色素瘤) 瘤发生的驱动因素.
- 虽然YAP的核保留机制已被理解,但TAZ的核保留机制尚未完全阐明.
研究的目的:
- 研究一种新型的乙化/脱乙化开关,调节TAZ亚细胞局部化.
- 确定这种TAZ调节在黑色素瘤瘤发生中的作用.
主要方法:
- 评估TAZ乙化和使用免疫沉/西欧斑点的相互作用.
- 量化了SIRT5活动,TAZ通过免疫光和TEAD转录活动的核定位.
- 在小鼠模型中评估了黑色素瘤细胞迁移,入侵和转移.
主要成果:
- 在K54处CBP乙化TAZ;在SIRT5处脱乙化TAZ.
- TAZ K54乙化通过LATS2相互作用促进细胞质保留.
- 通过SIRT5介导的脱乙基化增强了TAZ-TEAD相互作用,核保留和CTGF促进剂招募.
- 在体内,SIRT5的过度表达会导致黑色素瘤的转移,而黑色素瘤转移被脊髓瘤阻断.
结论:
- 一种涉及SIRT5介导的TAZ K54脱乙化的新机制控制了TAZ核保留.
- TAZ脱乙基化对CTGF表达具有重要意义,并促进黑色素瘤转移.
- SIRT5/TAZ轴对转移性黑色素瘤具有潜在的治疗点.
更多相关视频
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
6.9K
06:09Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
8.8K
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
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
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
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
The Intrinsic Apoptotic Pathway
6.6K
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...
6.6K
Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
