PTEN激活了伴侣介导的自,以调节新陈代谢
S Joseph Endicott1, Richard A Miller1,2
1Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Autophagy
|September 5, 2023
概括
PTEN蛋白激活伴侣介导自 (CMA) 调节新陈代谢和细胞生长. 这一途径可以通过控制关键代谢酶来延长寿命.
科学领域:
- 分子生物学分子生物学
- 细胞的新陈代谢
- 衰老研究研究 衰老研究
背景情况:
- PTEN (酸酶和素同类物) 是胰岛素-PI3K-AKT通路的关键调节剂,影响细胞生长和新陈代谢.
- 在各种癌症中,PTEN经常发生突变,作为瘤抑制剂.
- 有趣的是,PTEN过度表达与小鼠延长寿命有关.
研究的目的:
- 调查PTEN在激活伴侣介导自 (CMA) 中的作用.
- 确定PTEN介导的CMA激活如何影响像糖解和脂肪酸合成这样的代谢过程.
- 探索PTEN-CMA通路在调节健康和寿命方面的潜力.
主要方法:
- 利用小鼠肝脏模型和培养细胞来研究PTEN功能.
- 研究了PTEN在激活CMA时的必要性和充分性.
- 分析了PTEN过度表达对蛋白质降解和代谢酶活性的影响.
主要成果:
- 发现PTEN对于激活CMA在小鼠肝脏和培养细胞中既必要又足够.
- 过度表达PTEN导致蛋白质通过CMA被选择性降解.
- 这种选择性降解抑制了糖解和脂肪酸合成,表明代谢调节.
结论:
- 对CMA的PTEN激活是抑制关键代谢途径的关键机制.
- PTEN-CMA轴为调节新陈代谢和可能延长健康寿命提供了一个新的目标.
- 由PTEN下游的CMA调解的选择性蛋白质降解在代谢控制中起着重要作用.
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
The Unfolded Protein Response
4.7K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.7K
Autophagy
4.3K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.3K
Abnormal Proliferation
4.6K
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...
4.6K
The Proteasome
886
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
886


