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UTX 基因突变与人类癌症。

UTX Mutations in Human Cancer.

机构信息

Simpson Querrey Center for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Searle 6-512, 320 E. Superior St., Chicago, IL 60611, USA.

Simpson Querrey Center for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Searle 6-512, 320 E. Superior St., Chicago, IL 60611, USA.

出版信息

Cancer Cell. 2019 Feb 11;35(2):168-176. doi: 10.1016/j.ccell.2019.01.001.

DOI:10.1016/j.ccell.2019.01.001
PMID:30753822
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6589339/
Abstract

Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX, encoded by KDM6A) is a histone demethylase that targets di- and tri-methylated histone H3 lysine 27 (H3K27). UTX function has been linked to homeotic gene expression, embryonic development, and cellular reprogramming. UTX and its protein interactors within the COMPASS family, including the MLL3 and MLL4 lysine methyltransferases, are frequently mutated in multiple human cancers; however, the molecular basis of how these mutations contribute to oncogenesis remains unclear. Here, we discuss catalytic-dependent and -independent functions of UTX and its partners MLL3 and MLL4 as part of the COMPASS family during development and in oncogenesis.

摘要

X 染色体上普遍转录的四肽重复蛋白（UTX，由 KDM6A 编码）是一种组蛋白去甲基化酶，靶向二甲基化和三甲基化的组蛋白 H3 赖氨酸 27（H3K27）。UTX 的功能与同源盒基因表达、胚胎发育和细胞重编程有关。UTX 及其在 COMPASS 家族中的蛋白相互作用物，包括 MLL3 和 MLL4 赖氨酸甲基转移酶，在多种人类癌症中经常发生突变；然而，这些突变如何促进肿瘤发生的分子基础尚不清楚。在这里，我们讨论了 UTX 及其伙伴 MLL3 和 MLL4 在发育和致癌过程中作为 COMPASS 家族的一部分的催化依赖和非依赖功能。

相似文献

[1]
UTX Mutations in Human Cancer.

Cancer Cell. 2019-2-11

[2]
Cancer-derived UTX TPR mutations G137V and D336G impair interaction with MLL3/4 complexes and affect UTX subcellular localization.

Oncogene. 2020-2-18

[3]
Lysine Demethylase KDM6A in Differentiation, Development, and Cancer.

Mol Cell Biol. 2020-9-28

[4]
Increased expression of the histone H3 lysine 4 methyltransferase MLL4 and the histone H3 lysine 27 demethylase UTX prolonging the overall survival of patients with glioblastoma and a methylated MGMT promoter.

J Neurosurg. 2016-7-1

[5]
The cancer driver genes IDH1/2, JARID1C/ KDM5C, and UTX/ KDM6A: crosstalk between histone demethylation and hypoxic reprogramming in cancer metabolism.

Exp Mol Med. 2019-6-20

[6]
The H3K27me3 demethylase UTX in normal development and disease.

Epigenetics. 2014-2-21

[7]
The Histone Demethylase UTX Promotes Brown Adipocyte Thermogenic Program Via Coordinated Regulation of H3K27 Demethylation and Acetylation.

J Biol Chem. 2015-10-9

[8]
UTX and MLL4 coordinately regulate transcriptional programs for cell proliferation and invasiveness in breast cancer cells.

Cancer Res. 2014-2-3

[9]
Resetting the epigenetic balance of Polycomb and COMPASS function at enhancers for cancer therapy.

Nat Med. 2018-5-21

[10]
The histone demethylase UTX/KDM6A in cancer: Progress and puzzles.

Int J Cancer. 2019-1-28

引用本文的文献

[1]
KDM6A downregulation promotes tumor-prone cytokines expression in cancer-associated fibroblasts by activating enhancers.

Cell Death Dis. 2025-7-14

[2]
Phase Separation in Chromatin Organization and Human Diseases.

Int J Mol Sci. 2025-5-28

[3]
UTX Responds to Nanotopography to Suppress Macrophage Inflammatory Response by Remodeling H3K27me3 Modification.

Adv Sci (Weinh). 2025-8

[4]
UTX (KDM6A) promotes differentiation noncatalytically in somatic self-renewing epithelia.

Proc Natl Acad Sci U S A. 2025-5-20

[5]
Harnessing the Deubiquitinase USP1 for Targeted Protein Stabilization.

J Am Chem Soc. 2025-4-30

[6]
A conserved switch to less catalytically active Polycomb repressive complexes in non-dividing cells.

Cell Rep. 2025-1-28

[7]
Epigenetic Modifiers: Exploring the Roles of Histone Methyltransferases and Demethylases in Cancer and Neurodegeneration.

Biology (Basel). 2024-12-3

[8]
Membraneless organelles in health and disease: exploring the molecular basis, physiological roles and pathological implications.

Signal Transduct Target Ther. 2024-11-18

[9]
Neuroendocrine transdifferentiation in human cancer: molecular mechanisms and therapeutic targets.

MedComm (2020). 2024-10-4

[10]
Sex chromosome-encoded protein homologs: current progress and open questions.

Nat Struct Mol Biol. 2024-8

本文引用的文献

[1]
UTX is an escape from X-inactivation tumor-suppressor in B cell lymphoma.

Nat Commun. 2018-7-13

[2]
Resetting the epigenetic balance of Polycomb and COMPASS function at enhancers for cancer therapy.

Nat Med. 2018-5-21

[3]
Enhancer Logic and Mechanics in Development and Disease.

Trends Cell Biol. 2018-5-11

[4]
In vivo CRISPR screening unveils histone demethylase UTX as an important epigenetic regulator in lung tumorigenesis.

Proc Natl Acad Sci U S A. 2018-4-9

[5]
Comprehensive Characterization of Cancer Driver Genes and Mutations.

Cell. 2018-4-5

[6]
Loss of KDM6A Activates Super-Enhancers to Induce Gender-Specific Squamous-like Pancreatic Cancer and Confers Sensitivity to BET Inhibitors.

Cancer Cell. 2018-3-12

[7]
A Carcinogen-induced mouse model recapitulates the molecular alterations of human muscle invasive bladder cancer.

Oncogene. 2018-1-25

[8]
UTX/KDM6A Loss Enhances the Malignant Phenotype of Multiple Myeloma and Sensitizes Cells to EZH2 inhibition.

Cell Rep. 2017-10-17

[9]
Genome Regulation by Polycomb and Trithorax: 70 Years and Counting.

Cell. 2017-9-21

[10]
A UTX-MLL4-p300 Transcriptional Regulatory Network Coordinately Shapes Active Enhancer Landscapes for Eliciting Transcription.

Mol Cell. 2017-7-20

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