P19INK4d consists of five ankyrin repeats and controls the human cell cycle by inhibiting the cyclin D-dependent kinases 4 and 6. Posttranslational phosphorylation of p19INK4d has been described for Ser66 and Ser76. In the present study we show that mimicking the phosphorylation site of p19INK4d by a glutamate substitution at position 76 dramatically decreases the stability of the native but not an intermediate state. At body temperature the native conformation is completely lost and p19INK4d molecules exhibit the intermediate state as judged by kinetic and equilibrium analysis. High resolution NMR spectroscopy verified that the three C-terminal repeats remained folded in the intermediate state, whereas all cross-peaks of the two N-terminal repeats lost their native chemical shift. Molecular dynamic simulations of p19INK4d in different phosphorylation states revealed large-scale motions in phosphorylated p19INK4d, which cause destabilization of the interface between the second and third ankyrin repeat. Only doubly phosphorylated p19INK4d mimic mutants showed in vitro an increased accessibility for ubiquitination, which might be the signal for degradation in vivo.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/cb800219m | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Catalyst-Free Nitrogen Fixation by Microdroplets through a Radical-Mediated Disproportionation Mechanism under Ambient Conditions.
J Am Chem Soc
January 2025
State Key Laboratory of Physical Chemistry of Solid Surfaces, iChEM, College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen University, Xiamen 361005, China.
Nitrogen fixation is essential for the sustainable development of both human society and the environment. Due to the chemical inertness of the N≡N bond, the traditional Haber-Bosch process operates under extreme conditions, making nitrogen fixation under ambient conditions highly desirable but challenging. In this study, we present an ultrasonic atomizing microdroplet method that achieves nitrogen fixation using water and air under ambient conditions in a rationally designed sealed device, without the need for any catalyst.
View Article and Find Full Text PDFAtomically Dispersed FeMo Dual Sites for Enhanced Electrocatalytic Nitrogen Reduction.
ACS Appl Mater Interfaces
January 2025
State Key Laboratory of Fine Chemicals, Research and Development Center of Membrane Science and Technology, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China.
The electrocatalytic nitrogen reduction reaction (eNRR) is an attractive strategy for the green and distributed production of ammonia (NH); however, it suffers from weak N adsorption and a high energy barrier of hydrogenation. Atomically dispersed metal dual-site catalysts with an optimized electronic structure and exceptional catalytic activity are expected to be competent for knotty hydrogenation reactions including the eNRR. Inspired by the bimetallic FeMo cofactor in biological nitrogenase, herein, an atomically dispersed FeMo dual site anchored in nitrogen-doped carbon is proposed to induce a favorable electronic structure and binding energy.
View Article and Find Full Text PDFNeurological and Cognitive Effects of Hypothyroidism in Patients With Epilepsy: A Study on Anti-Seizure Medicines Therapy.
J Neurosci Res
January 2025
Department of Anaesthesiology and Intensive Care, Medical University Sofia, Sofia, Bulgaria.
The primary objective of this study was to examine neurological disorders and cognitive impairments in patients with secondary hypothyroidism and epilepsy undergoing treatment with antiepileptic medications. The study included 184 patients divided into three groups: Group 1 (subclinical hypothyroidism, n = 60), Group 2 (manifest hypothyroidism, n = 64), and Group 3 (control, n = 60). Patients in Group 2 received levothyroxine therapy (initial dose of 25 μg/day, titrated to 50-100 μg/day), while Groups 1 and 2 were treated with anti-seizure medications (valproic acid, 40 mg/kg/day).
View Article and Find Full Text PDFRecurrent Flow Update Model Using Image Pyramid Structure for 4K Video Frame Interpolation.
Sensors (Basel)
January 2025
School of Electrical and Electronic Engineering, Yonsei University, Seoul 03722, Republic of Korea.
Video frame interpolation (VFI) is a task that generates intermediate frames from two consecutive frames. Previous studies have employed two main approaches to extract the necessary information from both frames: pixel-level synthesis and flow-based methods. However, when synthesizing high-resolution videos using VFI, each approach has its limitations.
View Article and Find Full Text PDFMulti-Task Federated Split Learning Across Multi-Modal Data with Privacy Preservation.
Sensors (Basel)
January 2025
State Key Laboratory of Intelligent Vehicle Safety Technology, Chongqing 401133, China.
With the advancement of federated learning (FL), there is a growing demand for schemes that support multi-task learning on multi-modal data while ensuring robust privacy protection, especially in applications like intelligent connected vehicles. Traditional FL schemes often struggle with the complexities introduced by multi-modal data and diverse task requirements, such as increased communication overhead and computational burdens. In this paper, we propose a novel privacy-preserving scheme for multi-task federated split learning across multi-modal data (MTFSLaMM).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!