由AAK1激活介导的铁贩运驱动铁细胞死亡
Li-Chao Li1, Zhi-Peng Ye2, Ying Xiao1,3
1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
Nature communications
|December 17, 2025
概括
蛋白激酶CβII (PKCβII) 通过激活AAK1,促进转移林受体1 (TFR1) 内细胞分裂,通过激活AAK1来调节铁灭过程中的铁吸收. 这一途径对铁亡至关重要,并影响乳腺癌的进展.
科学领域:
- 细胞生物学 细胞生物学
- 分子机制的分子机制
- 癌症研究 癌症研究
背景情况:
- 铁对于铁亡,即受调节的细胞死亡途径至关重要.
- 细胞铁平衡对于铁灭至关重要,但在这个过程中铁的吸收机制尚未完全理解.
研究的目的:
- 阐明调节铁灭过程中细胞铁吸收的分子机制.
- 为了确定参与ferroptosis中的转移林受体1 (TFR1) 内细胞结合的关键蛋白质.
主要方法:
- 激酶测定以确定PKCβII作为关键调节剂.
- 对AAK1和AP2M1.1.的酸化位点分析.
- 细胞铁吸收的测量.细胞铁吸收的测量.
- 在使用乳腺瘤模型的体内研究.
主要成果:
- PKCβII可酸化并激活AAK1,后者反过来可酸化AP2M1.1.
- 激活的AAK1促进了TFR1的克拉特林介导的内细胞分裂,增加了细胞铁水平.
- 抑制AAK1酸化抑制铁亡并增强乳腺瘤的生长.
结论:
- 确定PKCβII-AAK1-AP2M1通路是铁灭过程中细胞铁吸收的关键调节者.
- 这一途径影响乳腺癌的预后,并代表了潜在的治疗标.
相关概念视频
Necrosis
6.2K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
6.2K
Overview of Cell Death
9.3K
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
9.3K
The Intrinsic Apoptotic Pathway
8.2K
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...
8.2K
Autophagic Cell Death
4.3K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.3K
The Early Endosome: Endocytosis of Transferrin
4.6K
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
4.6K
The Extrinsic Apoptotic Pathway
8.0K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
8.0K

