更新于：2024-09-19

ULK3

更新于：2024-09-19

基本信息

别名

DKFZP434C131、FLJ90566、Serine/threonine-protein kinase ULK3

+ [4]

简介

Serine/threonine protein kinase that acts as a regulator of Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative regulator of SHH signaling in the absence of SHH ligand: interacts with SUFU, thereby inactivating the protein kinase activity and preventing phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively regulates SHH signaling in the presence of SHH: dissociates from SUFU, autophosphorylates and mediates phosphorylation of GLI2, activating it and promoting its nuclear translocation. Phosphorylates in vitro GLI2, as well as GLI1 and GLI3, although less efficiently. Also acts as a regulator of autophagy: following cellular senescence, able to induce autophagy.

关联

项与 ULK3 相关的药物

MA9-060

靶点

BRD4 x ULK3

作用机制

BRD4抑制剂 [+1]

在研机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

原研机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

在研适应症

多发性骨髓瘤 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 ULK3 相关的临床结果

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100 项与 ULK3 相关的转化医学

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0 项与 ULK3 相关的专利（医药）

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项与 ULK3 相关的文献（医药）

2024-05-01·Journal of Assisted Reproduction and Genetics

The chromosomal characteristics of spontaneous abortion and its potential associated copy number variants and genes

Article

作者: Wu, Jianli ; Feng, Ling ; Sha, Menghan ; Chen, Suhua ; Sun, Yanan ; Qin, Yu ; Touch, Koksear ; Xiao, Juan ; Wu, Yuanyuan ; Zhang, Shunran

PURPOSEThis study aimed to investigate the correlation between chromosomal abnormalities in spontaneous abortion with clinical features and seek copy number variations (CNVs) and genes that might be connected to spontaneous abortion.METHODSOver 7 years, we used CNV-seq and STR analysis to study POCs, comparing chromosomal abnormalities with clinical features and identifying critical CNVs and genes associated with spontaneous abortion.RESULTSTotal chromosomal variants in the POCs were identified in 66.8% (2169/3247) of all cases, which included 45.2% (1467/3247) numerical abnormalities and 21.6% (702/3247) copy number variants (CNVs). Chromosome number abnormalities, especially aneuploidy abnormalities, were more pronounced in the group of mothers aged ≥ 35 years, the early miscarriage group, and the chorionic villi group. We further analyzed 212 pathogenic and likely pathogenic CNVs in 146 POCs as well as identified 8 statistically significant SORs through comparison with both a healthy population and a group of non-spontaneously aborted fetuses. Our analysis suggests that these CNVs may play a crucial role in spontaneous abortion. Furthermore, by utilizing the RVIS score and MGI database, we identified 86 genes associated with spontaneous abortion, with particular emphasis on PARP6, ISLR, ULK3, FGFRL1, TBC1D14, SCRIB, and PLEC.CONCLUSIONWe found variability in chromosomal abnormalities across clinical features, identifying eight crucial copy number variations (CNVs) and multiple key genes that may be linked to spontaneous abortion. This research enhances the comprehension of genetic factors contributing to spontaneous abortion.

2024-01-01·Cell Genomics

Multi-ancestry genetic analysis of gene regulation in coronary arteries prioritizes disease risk loci

Article

作者: Wong, Doris ; Miller, Clint L ; Leeper, Nicholas J ; Peyser, Patricia A ; Farber, Emily ; Björkegren, Johan L M ; Khan, Mohammad Daud ; Ma, Wei Feng ; Barrientos, Nelson B ; Kovacic, Jason C ; Turner, Adam W ; Hodonsky, Chani J ; Onengut-Gumuscu, Suna ; van der Laan, Sander W ; Methorst, Ruben ; Mosquera, Jose Verdezoto ; Auguste, Gaëlle ; Kavousi, Maryam ; Ma, Lijiang ; Lopez, Nicolas G

Genome-wide association studies (GWASs) have identified hundreds of risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in GWASs, and the causal gene-regulatory mechanisms of these risk loci during atherosclerosis remain unclear. We incorporated local ancestry and haplotypes to identify quantitative trait loci for expression (eQTLs) and splicing (sQTLs) in coronary arteries from 138 ancestrally diverse Americans. Of 2,132 eQTL-associated genes (eGenes), 47% were previously unreported in coronary artery; 19% exhibited cell-type-specific expression. Colocalization revealed subgroups of eGenes unique to CAD and blood pressure GWAS. Fine-mapping highlighted additional eGenes, including TBX20 and IL5. We also identified sQTLs for 1,690 genes, among which TOR1AIP1 and ULK3 sQTLs demonstrated the importance of evaluating splicing to accurately identify disease-relevant isoform expression. Our work provides a patient-derived coronary artery eQTL resource and exemplifies the need for diverse study populations and multifaceted approaches to characterize gene regulation in disease processes.

2024-01-01·Iranian journal of basic medical sciences

Comprehensive analysis of autophagy associated genes and immune infiltrates in cervical cancer.

Article

作者: Yao, Desheng ; Li, Shuzhen ; Gao, Kun

ObjectivesCervical cancer (CC) is the most common gynecological malignant tumor and the fourth leading cause of cancer-related death in women. The progression of CC is significantly affected by autophagy. Our objective was to use bioinformatics analysis to explore the expression, prognostic significance, and immune infiltration of autophagy-related genes in CC.Materials and MethodsWe identified a set of autophagy-related differentially expressed genes (ARDEGs) from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ARDEGs were further validated by The Human Protein Atlas (HPA), GSE52903, and GSE39001 dataset. Hub genes were found by the STRING network and Cytoscape. We performed Gene Set Enrichment Analysis (GSEA), Gene ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and immune infiltration analysis to further understand the functions of the hub genes. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) were used to check the hub genes.ResultsA total of 10 up-regulated (CXCR4, BAX, SPHK1, EIF2AK2, TBK1, TNFSF10, ITGB4, CDKN2A, IL24, and BIRC5) and 19 down-regulated (PINK1, ATG16L2, ATG4D, IKBKE, MLST8, MAPK3, ERBB2, ULK3, TP53INP2, MTMR14, BNIP3, FOS, CCL2, FAS, CAPNS1, HSPB8, PTK6, FKBP1B , and DNAJB1) ARDEGs were identified. The ARDEGs were enriched in cell growth, apoptosis, human papillomavirus infection, and cytokine-mediated. Then, we found that low expression of MAPK3 was associated with poor prognosis in CC patients and was significantly enriched in immune pathways. In addition, the expression of MAPK3 was significantly positively correlated with the infiltration levels of macrophages, B cells, mast cell activation, and cancer-associated fibroblasts. Furthermore, MAPK3 was positively correlated with LGALS9, and negatively correlated with CTLA4 and CD40.ConclusionOur results show that MAPK3 can be used as a new prognostic biomarker to predict the prognosis of patients with CC.