Ubiquitin C-terminal Hydrolase Isozyme L1 is Associated with Shelterin Complex at Interstitial Telomeric Sites

Overview

Journal Epigenetics Chromatin

Publisher Biomed Central

Specialties Biochemistry
Genetics

Date 2017 Nov 12

PMID 29126443

Citations 3

Authors

Aleksandar Ilic

Sumin Lu

Vikram Bhatia

Farhana Begum

Thomas Klonisch

Prasoon Agarwal

Wayne Xu

James R Davie

Affiliations

Soon will be listed here.

Abstract

Background: Ubiquitin C-terminal hydrolase isozyme L1 (UCHL1) is primarily expressed in neuronal cells and neuroendocrine cells and has been associated with various diseases, including many cancers. It is a multifunctional protein involved in deubiquitination, ubiquitination and ubiquitin homeostasis, but its specific roles are disputed and still generally undetermined.

Results: Herein, we demonstrate that UCHL1 is associated with genomic DNA in certain prostate cancer cell lines, including DU 145 cells derived from a brain metastatic site, and in HEK293T embryonic kidney cells with a neuronal lineage. Chromatin immunoprecipitation and sequencing revealed that UCHL1 localizes to TTAGGG repeats at telomeres and interstitial telomeric sequences, as do TRF1 and TRF2, components of the shelterin complex. A weak or transient interaction between UCHL1 and the shelterin complex was confirmed by immunoprecipitation and proximity ligation assays. UCHL1 and RAP1, also known as TERF2IP and a component of the shelterin complex, were bound to the nuclear scaffold.

Conclusions: We demonstrated a novel feature of UCHL1 in binding telomeres and interstitial telomeric sites.

Citing Articles

DNA-methylation and genomic copy number in primary tumors and corresponding lymph node metastases in prostate cancer from patients with low and high Gleason score.

Unger K, Hess J, Link V, Buchner A, Eze C, Li M Clin Transl Radiat Oncol. 2023; 39:100586.

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At the Beginning of the End and in the Middle of the Beginning: Structure and Maintenance of Telomeric DNA Repeats and Interstitial Telomeric Sequences.

Aksenova A, Mirkin S Genes (Basel). 2019; 10(2).

PMID: 30764567 PMC: 6410037. DOI: 10.3390/genes10020118.

UCH-L1 bypasses mTOR to promote protein biosynthesis and is required for MYC-driven lymphomagenesis in mice.

Hussain S, Bedekovics T, Liu Q, Hu W, Jeon H, Johnson S Blood. 2018; 132(24):2564-2574.

PMID: 30257881 PMC: 6293873. DOI: 10.1182/blood-2018-05-848515.

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