PHAP蛋白和prothymosin-alpha在死亡调节途径中的独特作用
Xuejun Jiang1, Hyun-Eui Kim, Hongjun Shu
1Howard Hughes Medical Institute, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
概括
一种新的小分子,PETCM,通过调节PHAP/ProT通路,激活癌细胞中的caspase-3. 这一途径调节了亡,其中ProT抑制和PHAP促进酶激活.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 细胞亡是一个关键的细胞过程,在癌症中经常受到失调.
- 线粒体启动的酶激活是亡的关键途径.
- 识别这种途径的调节者可以揭示新的治疗点.
研究的目的:
- 为了识别激活癌细胞中caspase-3的小分子.
- 阐明调节线粒体启动的酶激活的分子途径.
- 了解PHAP蛋白和prothymosin-alpha在亡中的作用.
主要方法:
- 高通量选用于识别caspase-3激活剂.
- 生物化学分化以隔离路径组件.
- 评估基因功能的RNA干扰.
- 卡斯帕斯活性测定.
主要成果:
- 一个小分子,α-(三甲基) -4-皮里迪尼醇 (PETCM),被确定为一个caspase-3激活剂.
- PETCM调节了一条涉及瘤抑制剂PHAP蛋白和coproteinprothymosin-alpha (ProT) 的途径.
- PHAP促进酶-9的激活,而ProT通过阻断细胞细胞形成来抑制它;PETCM缓解了ProT的抑制.
- 消除了对紫外线诱导的亡敏感的细胞,并绕过了对PETCM的需求.
结论:
- 通过缓解由蛋白质T介导的代细胞形成的抑制,PETCM激活了caspase-3.
- PHAP/ProT通路是线粒体启动的亡的关键调节者.
- 瘤蛋白质蛋白质和瘤抑制剂PHAP在调节亡中起着相反的作用.
相关概念视频
Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
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...
Protein Denaturation
The function of proteins depends on their native three-dimensional structure, which is dictated by the amino acid sequence of the specific protein. Folding of the polypeptide chain takes place under specific conditions that energetically favor the folded conformation. In contrast, protein denaturation occurs spontaneously under unfavorable conditions that disrupt the integrity of the folded conformation. Thus, the chemical and physical environment of a protein, such as significant changes in pH...
Bacterial Protein Maturation
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...


