4.8 Article

MDM2 E3 ligase-mediated ubiquitination and degradation of HDAC1 in vascular calcification

期刊

NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms10492

关键词

-

资金

  1. Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education [2015R1A2A1A05001708]
  2. National Research Foundation of Korea grant (MRC) - Korean government (MSIP) [2011-0030132]
  3. Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A121260, A111345]
  4. National Research Foundation of Korea [2015R1A2A1A05001708] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

向作者/读者索取更多资源

Vascular calcification (VC) is often associated with cardiovascular and metabolic diseases. However, the molecular mechanisms linking VC to these diseases have yet to be elucidated. Here we report that MDM2-induced ubiquitination of histone deacetylase 1 (HDAC1) mediates VC. Loss of HDAC1 activity via either chemical inhibitor or genetic ablation enhances VC. HDAC1 protein, but not mRNA, is reduced in cell and animal calcification models and in human calcified coronary artery. Under calcification-inducing conditions, proteasomal degradation of HDAC1 precedes VC and it is mediated by MDM2 E3 ubiquitin ligase that initiates HDAC1 K74 ubiquitination. Overexpression of MDM2 enhances VC, whereas loss of MDM2 blunts it. Decoy peptide spanning HDAC1 K74 and RG 7112, an MDM2 inhibitor, prevent VC in vivo and in vitro. These results uncover a previously unappreciated ubiquitination pathway and suggest MDM2-mediated HDAC1 ubiquitination as a new therapeutic target in VC.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Review Pharmacology & Pharmacy

The roles of non-coding RNAs in vascular calcification and opportunities as therapeutic targets

Juhee Ryu, Youngkeun Ahn, Hyun Kook, Young-Kook Kim

Summary: This article reviews the role and therapeutic implications of non-coding RNAs (ncRNAs) in vascular calcification (VC). Studies suggest that ncRNAs, including miRNAs, lncRNAs, and circRNAs, play important roles in regulating VC and may be useful in clinical diagnosis and treatment.

PHARMACOLOGY & THERAPEUTICS (2021)

Article Medicine, Research & Experimental

miR-27a-3p Targets ATF3 to Reduce Calcium Deposition in Vascular Smooth Muscle Cells

Nakwon Choe, Duk-Hwa Kwon, Juhee Ryu, Sera Shin, Hye Jung Cho, Hosouk Joung, Gwang Hyeon Eom, Youngkeun Ahn, Woo Jin Park, Kwang-Il Nam, Young-Kook Kim, Hyun Kook

MOLECULAR THERAPY-NUCLEIC ACIDS (2020)

Article Medicine, Research & Experimental

HDAC5 inhibition reduces angiotensin II-induced vascular contraction, hypertrophy, and oxidative stress in a mouse model

Liyan Bai, Hae Jin Kee, Sin Young Choi, Young Mi Seok, Gwi Ran Kim, Seung-Jung Kee, Hyun Kook, Myung Ho Jeong

Summary: The genetic deletion of HDAC5 and treatment with class IIa HDAC inhibitors can prevent increases in blood pressure and arterial wall thickness induced by Ang II. HDAC5 plays a role in vascular contraction and hypertrophy, and its inhibition may be a potential target for hypertension treatment.

BIOMEDICINE & PHARMACOTHERAPY (2021)

Article Cardiac & Cardiovascular Systems

S-Nitrosylation of Histone Deacetylase 2 by Neuronal Nitric Oxide Synthase as a Mechanism of Diastolic Dysfunction

Somy Yoon, Mira Kim, Hangyeol Lee, Gaeun Kang, Kenneth Bedi, Kenneth B. Margulies, Rajan Jain, Kwang-Il Nam, Hyun Kook, Gwang Hyeon Eom

Summary: The study reveals that neuronal nitric oxide synthase induces diastolic dysfunction by S-nitrosylation of HDAC2, suggesting a new therapeutic platform for refractory heart failure with preserved ejection fraction.

CIRCULATION (2021)

Article Biochemistry & Molecular Biology

SRF is a nonhistone methylation target of KDM2B and SET7 in the regulation of skeletal muscle differentiation

Duk-Hwa Kwon, Joo-Young Kang, Hosouk Joung, Ji-Young Kim, Anna Jeong, Hyun-Ki Min, Sera Shin, Yun-Gyeong Lee, Young-Kook Kim, Sang-Beom Seo, Hyun Kook

Summary: The balance between KDM2B and SET7, two competing enzymes that respectively inhibit and activate the same gene-regulating protein SRF, plays a critical role in skeletal muscle cell differentiation. KDM2B inhibits cell differentiation by demethylating SRF, while SET7 activates differentiation by methylating SRF. This study reveals SRF as a novel target of KDM2B and provides insights into skeletal muscle development in health and disease.

EXPERIMENTAL AND MOLECULAR MEDICINE (2021)

Article Biochemistry & Molecular Biology

Bifunctional Role of CrkL during Bone Remodeling

Jung Ha Kim, Kabsun Kim, Inyoung Kim, Semun Seong, Hyun Kook, Kyung Keun Kim, Jeong-Tae Koh, Nacksung Kim

Summary: CrkL regulates the coupling signals between osteoblasts and osteoclasts by decreasing RANKL expression, which plays a crucial role in bone homeostasis by inhibiting both osteoblast-dependent osteoclast differentiation and osteoclast-dependent osteoblast differentiation.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Biochemistry & Molecular Biology

P300/CBP-Associated Factor Activates Cardiac Fibroblasts by SMAD2 Acetylation

Yongwoon Lim, Anna Jeong, Duk-Hwa Kwon, Yeong-Un Lee, Young-Kook Kim, Youngkeun Ahn, Taewon Kook, Woo-Jin Park, Hyun Kook

Summary: Various heart diseases lead to ineffective cardiac contraction, with cardiac fibrosis being a contributing factor. PCAF plays a key role in the activation of cardiac fibroblasts during cardiac remodeling.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Biochemistry & Molecular Biology

Regulation of MDM2 E3 ligase-dependent vascular calcification by MSX1/2

Duk-Hwa Kwon, Nakwon Choe, Sera Shin, Juhee Ryu, Nacksung Kim, Gwang Hyeon Eom, Kwang-Il Nam, Hyung Seok Kim, Youngkeun Ahn, Young-Kook Kim, Woo Jin Park, Susan M. Mendrysa, Hyun Kook

Summary: The study revealed the driver and activation pathway of vascular calcification, causing severe complications in patients with cardiovascular and renal diseases, potentially providing valuable information for novel therapeutic strategies targeting related conditions.

EXPERIMENTAL AND MOLECULAR MEDICINE (2021)

Article Surgery

Anatomical Characteristics of the Anterior Jugular Vein and Its Clinical Relevance

Dong Hoon Lee, Young-Suk Cho, Wook Hyun Jung, Sang Chul Lim, Kwang Il Nam

Summary: The study conducted an anatomical analysis of the anterior jugular vein in Koreans, finding that a safety zone at the main landmark of the neck could be used to prevent damage to the AJV.

JOURNAL OF CRANIOFACIAL SURGERY (2022)

Article Anatomy & Morphology

Distribution of the tensor of the vastus intermedius

Hyeng-Kyu Park, Jae-Young Han, Young-Suk Cho, Kwang-Il Nam

Summary: The tensor of the vastus intermedius (TVI) originated from the anteroinferior greater trochanter and inserts into the upper patella. It has been overlooked but warrants more research due to the development of micro-surgery and detailed rehabilitation treatments.

CLINICAL ANATOMY (2023)

Article Respiratory System

Patients with Epiglottic Collapse Are Less Adherent to Autotitrating Positive Airway Pressure Therapy for Obstructive Sleep Apnea

Chung Man Sung, Hong Chan Kim, Jisun Kim, Jae Gu Kim, Sang Chul Lim, Min-Ho Shin, Kwangil Nam, Jongho Lee, Daniel Vena, David P. White, Hyung Chae Yang, Andrew Wellman

Summary: This study analyzed adherence to autotitrating positive airway pressure (APAP) treatment in patients with epiglottic collapse. It found that patients with epiglottic collapse had a higher APAP adherence failure rate and lower usage time compared to patients without epiglottic collapse. These patients also had a lower body mass index, which is an unfavorable predictor of APAP adherence.

ANNALS OF THE AMERICAN THORACIC SOCIETY (2022)

Article Allergy

Intralymphatic Administration of Metagonimus yokogawai-Extracted Protein Attenuates Experimental Murine Allergic Rhinitis Model

Hyung Chae Yang, Eun Jeong Won, Moon-Ju Kim, Chung Man Sung, Joon Haeng Rhee, Kwang Il Nam

Summary: The intralymphatic injection of Metagonimus yokogawai extract protein (My-TP) was shown to reduce allergic symptoms and eosinophil infiltration in the nasal mucosa of OVA-sensitized allergic rhinitis mice. Additionally, My-TP treatment group exhibited significantly decreased levels of OVA-specific IgE and white blood cell counts in nasal lavage. This study suggests a potential therapeutic effect of My-TP in allergic rhinitis by modulating the Treg/Th2 balance.

INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY (2021)

Article Materials Science, Multidisciplinary

Soft Magnetic Pillars to Secure an Upper Airway for the Relief of Obstructive Sleep Apnea

Hyunjong Kim, Chung Man Sung, Hunpyo Ju, Hyeongoh Park, Jinmo Jeong, Kwang Il Nam, Hyung Chae Yang, Jongho Lee

ADVANCED MATERIALS TECHNOLOGIES (2020)

Meeting Abstract Allergy

Attenuation of allergic rhinitis inflammation by intra lymphatic administration of Metagonimus yokogawai-extracted protein

Hyung Chae Yang, Eun Jeong Won, Chungman Sung, Sang Chul Lim, Kwang Il Nam

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2020)

暂无数据