װ ȭа ΰ

Content on this page requires a newer version of Adobe Flash Player.

Get Adobe Flash player

 
ۼ : 15-11-26 09:35
[15.11] - A chemical inhibitor of the Skp2/p300 interaction that promotes p53-mediated apoptosis
-
 ۾ :
ȸ : 1,449  

A chemical inhibitor of the Skp2/p300 interaction that promotes p53-mediated apoptosis

M. Oh, J. H. Lee, H. Moon, Y.-J. Hyun, and H. S. Lim

Skp2 is thought to have two critical roles in tumorigenesis. As part of SCFSkp2 ubiquitin ligase, Skp2 drives the cell cycle by mediating the degradation of cell cycle proteins. Besides the proteolytic activity, Skp2 blocks p53-mediated apoptosis by outcompeting p53 for binding p300. Here we exploit the Skp2/p300 interaction as a new target for Skp2 inhibition. An affinity-based high-throughput screening of a combinatorial cyclic peptoid library identified an inhibitor that binds to Skp2 and interferes with the Skp2/p300 interaction. We show that antagonizing the Skp2/p300 interaction by the inhibitor leads to p300-mediated p53 acetylation, resulting in p53-mediated apoptosis in cancer cells, without affecting Skp2 proteolytic activity. Our results suggest that inhibition of the Skp2/p300 interaction has a great potential as a new anticancer strategy, and our Skp2 inhibitor can be developed as a chemical probe to delineate Skp2 non-proteolytic function in tumorigenesis.

ܹ ȣۿ پ Ǵ ˷ ִ. Skp2 ܹ پ ϼ ٹǸ ܹ ȣۿ ϼ ڷ ˷ ִ. ʰ ũ ̿Ͽ Skp2 ߱Ͽ. ȭչ skp2/p300 ܹ ȣۿ ϸ, ̷ ϼ ϴ p53 ܹ Ƽƿȭ ȭ ϴ . ȭչ ġ ʴ ݸ پ ϼ ȿ ϴ ο ׾μ 缺 . Skp2/p300 ܹ ȣۿ ׾ ǥ ִٴ ó , ο ǥ׾ ߿ ū ǰ ִ.


 
 

Total 73
ȣ     ۾ ¥ ȸ
58 [15.11] - A chemical inhibitor of the Skp2/p300 interaction that promotes p53-mediated apoptosis 11-26 1450
57 [15.11] ⹮ - Hydrolytic Transformation of Microporous Metal–Organic Frameworks to Hierarchical Micro- and Mesoporous MOFs 11-11 1294
56 [15.8] ⹮ - Porphyrin Boxes: Rationally Designed Porous Organic Cages 09-07 1309
55 [15.7] ⹮ - High Affinity Host−Guest FRET Pair for Single-Vesicle Content-Mixing Assay: Observation of Flickering Fusion Events 09-07 1504
54 [15.4] ⹮ - Self-assembly of Nanostructured Materials through Irreversible Covalent Bond Formation 09-07 1469
53 [15.07] ڹ - High-Conductivity Two-Dimensional Polyaniline Nanosheets Developed on Ice Surfaces 06-29 1499
52 [15.06]ö -Germanium Silicon Alloy Anode Material Capable of Tunable Overpotential by Nanoscale Si Segregation 06-29 1220
51 [15.06]ڹ - Synthesis of Three-Dimensionally Interconnected Sulfur-Rich Polymers for Cathode Materials of High-Rate Lithium-Sulfur Batteries 06-15 1412
50 [15.05]ȱѱ -Two-Photon Absorbing Dyes with Minimal Autofluorescence in Tissue Imaging 06-04 1178
49 [15.05]ȱѱ -A Structural Remedy toward Bright Dipolar Fluorophores in Aqueous Media 05-27 1780
48 [15.04] -N-Heterocyclic Carbene Nitric Oxide Radicals 05-06 1515
47 [15.04]ؿ -Cytosolic targeting factor AKR2A captures chloroplast outer membrane-localized client proteins at the ribosome during translation 04-23 1507
46 [15.02]⹮ -Reversible Morphological Transformation between Polymer Nanocapsules and Thin Films through Dynamic Covalent Self-Assembly 02-09 1291
45 [14.09]ؿ -Reading Single DNA with DNA Polymerase Followed by Atomic Force Microscopy 09-18 1611
44 [14.08]ö _Crystallization-Induced Properties from Morphology-Controlled Organic Crystals 08-21 1553
 1  2  3  4  5  

Content on this page requires a newer version of Adobe Flash Player.

Get Adobe Flash player