Ubiquitin C-terminal hydrolase isozyme L1 is associated with shelterin complex at interstitial telomeric sites

Autor: Aleksandar Ilic, Sumin Lu, Vikram Bhatia, Farhana Begum, Thomas Klonisch, Prasoon Agarwal, Wayne Xu, James R. Davie
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Epigenetics & Chromatin, Vol 10, Iss 1, Pp 1-16 (2017)
Druh dokumentu: article
ISSN: 1756-8935
DOI: 10.1186/s13072-017-0160-2
Popis: 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.
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