Last update 01 Nov 2024

KLHL18

Last update 01 Nov 2024

Basic Info

Synonyms

FLJ13703, kelch like family member 18, Kelch-like protein 18

+ [2]

Introduction

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis (PubMed:23213400). The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination of AURKA leading to its activation at the centrosome which is required for initiating mitotic entry (PubMed:23213400). Regulates light-and dark-dependent alpha-transducin localization changes in rod photoreceptors through UNC119 ubiquitination and degradation (By similarity). Preferentially ubiquitinates the unphosphorylated form of UNC119 over the phosphorylated form (By similarity). In the presence of UNC119, under dark-adapted conditions alpha-transducin mislocalizes from the outer segment to the inner part of rod photoreceptors which leads to decreased photoreceptor damage caused by light (By similarity).

Drugs associated with KLHL18

CN114369600

Patent Mining

Target

KLHL18

Mechanism-

Active Org.

Fudan University Affiliated Eye & Ent Hospital

Originator Org.

Fudan University Affiliated Eye & Ent Hospital

Active Indication

Neurologic Manifestations

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with KLHL18

100 Translational Medicine associated with KLHL18

0 Patents (Medical) associated with KLHL18

Literatures (Medical) associated with KLHL18

01 Sep 2023·Placenta

Epigenetic modifications appear in the human placenta following anxiety and depression during pregnancy

Article

Author: Josefsson, Ann ; Martinez, Cristina A ; Theodorsson, Elvar ; Marteinsdottir, Ina ; Sydsjö, Gunilla ; Rodriguez-Martinez, Heriberto

INTRODUCTIONThe future health of the offspring can be influenced by longstanding maternal anxiety and depression disorders during pregnancy. The present study aimed to explore the effect of psychiatric disorders during pregnancy on placental epigenetics.METHODSWe measured DNA methylation patterns in term-placentas of women either suffering longstanding anxiety and depression symptoms (Index group, with overt symptoms), or a healthy population (Control, none/only mild symptoms). Whole genome DNA methylation profiling was performed using the TruSeq® Methyl Capture EPIC Library Prep Kit (Illumina, San Diego, CA, USA) for library preparation and NGS technology for genomic DNA sequencing.RESULTSThe results of high-throughput DNA methylation analysis revealed that the Index group had differential DNA methylation at epigenome-wide significance (p < 0.05) in 226 genes in the placenta. Targeted enrichment analyses identified hypermethylation of genes associated with psychiatric disorders (BRINP1, PUM1), and ion homeostasis (COMMD1), among others. The ECM (extracellular matrix)-receptor interaction pathway was significantly dysregulated in the Index group compared to the Control. In addition, DNA methylation/mRNA integration analyses revealed that four genes with key roles in neurodevelopment and other important processes (EPB41L4B, BMPR2, KLHL18, and UBAP2) were dysregulated at both, DNA methylation and transcriptome levels in the Index group compared to Control.DISCUSSIONThe presented results increase our understanding of how maternal psychiatric disorders may affect the newborn through placental differential epigenome, suggesting DNA methylation status as a biomarker when aiming to design new preventive techniques and interventions.

01 Jan 2021·Reproductive SciencesQ3 · MEDICINE

Association of Maternal DNA Methylation and Offspring Birthweight

Q3 · MEDICINE

Article

Author: Pershagen, Goran ; Chen, Su ; Andolf, Ellika ; Hedman, Anna ; Arshad, Syed Hasan ; Kere, Juha ; Jiang, Yu ; Holloway, John W ; Karmaus, Wilfried ; Mukherjee, Nandini ; Kheirkhah Rahimabad, Parnian ; Gruzieva, Olena ; Almqvist, Catarina

This study aims to evaluate the association of maternal DNA methylation (DNAm) during pregnancy and offspring birthweight. One hundred twenty-two newborn-mother dyads from the Isle of Wight (IOW) cohort were studied to identify differentially methylated cytosine-phosphate-guanine sites (CpGs) in maternal blood associated with offspring birthweight. Peripheral blood samples were drawn from mothers at 22-38 weeks of pregnancy for epigenome-wide DNAm assessment using the Illumina Infinium HumanMethylation450K array. Candidate CpGs were identified using a course of 100 repetitions of a training and testing process with robust regressions. CpGs were considered informative if they showed statistical significance in at least 80% of training and testing samples. Linear mixed models adjusting for covariates were applied to further assess the selected CpGs. The Swedish Born Into Life cohort was used to replicate our findings (n = 33). Eight candidate CpGs corresponding to the genes LMF1, KIF9, KLHL18, DAB1, VAX2, CD207, SCT, SCYL2, DEPDC4, NECAP1, and SFRS3 in mothers were identified as statistically significantly associated with their children's birthweight in the IOW cohort and confirmed by linear mixed models after adjusting for covariates. Of these, in the replication cohort, three CpGs (cg01816814, cg23153661, and cg17722033 with p values = 0.06, 0.175, and 0.166, respectively) associated with four genes (LMF1, VAX2, CD207, and NECAP1) were marginally significant. Biological pathway analyses of three of the genes revealed cellular processes such as endocytosis (possibly sustaining an adequate maternal-fetal interface) and metabolic processes such as regulation of lipoprotein lipase activity (involved in providing substrates for the developing fetus). Our results contribute to an epigenetic understanding of maternal involvement in offspring birthweight. Measuring DNAm levels of maternal CpGs may in the future serve as a diagnostic tool recognizing mothers at risk for pregnancies ending with altered birthweights.

01 Dec 2020·Cell & BioscienceQ3 · BIOLOGY

KLHL18 inhibits the proliferation, migration, and invasion of non-small cell lung cancer by inhibiting PI3K/PD-L1 axis activity

Q3 · BIOLOGY

ArticleOA

Author: Xu, Yitong ; Zhang, Yao ; Jiang, Xizi ; Wang, Qiongzi ; Su, Hongbo ; Wang, Huanxi ; Wudu, Muli ; Cheng, Yu ; Guan, Jingqian ; Liu, Zongang ; Sun, Limei ; Qiu, Xueshan ; Guo, Yuanzi ; Jiang, Jun ; Hu, Yujiao ; Jiang, Lihong ; Zhang, Bo ; Ren, Hongjiu

AbstractBackgroundThe expression of Kelch-like protein 18 (KLHL18) in non-small cell lung cancer (NSCLC) is lower than that in normal lung tissue according to the Gene Expression Profiling Interactive Analysis database. KLHL18 is a BTB domain protein and binds cullin 3 (CUL3). However, whether this complex participates in ubiquitination-mediated protein degradation in NSCLC is unclear. Therefore, we aimed to investigate the role of KLHL18 in human NSCLC cells.ResultsWe found that KLHL18 is downregulated in cancer cells and is associated with poor prognosis. Further, its expression was significantly associated with tumor node metastasis (TNM) stage, lymph node metastasis, and tumor size. In vitro analysis of NSCLC cells showed that overexpressing KLHL18 inhibited cell proliferation, migration, and invasion. We found that the tumor-inhibitory effect of the KLHL18 protein was achieved by promoting the ubiquitination and degradation of phosphatidylinositol 3-kinase (PI3K) p85α and inhibiting the expression of PD-L1 protein, ultimately preventing tumor cell immune escape.ConclusionsOur results identified the tumor-suppressive mechanism of KLHL18 and suggested that it is closely related to NSCLC occurrence and development. Further investigation of the underlying mechanism may provide new targets for NSCLC treatment.

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KLHL18

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