@article{feaf41e9eacb4612b3ccc2ea8928d76b,
title = "BLM Potentiates c-Jun Degradation and Alters Its Function as an Oncogenic Transcription Factor",
abstract = "Mutations in BLM helicase predispose Bloom syndrome (BS) patients to a wide spectrum of cancers. We demonstrate that MIB1-ubiquitylated BLM in G1 phase functions as an adaptor protein by enhancing the binding of transcription factor c-Jun and its E3 ligase, Fbw7α. BLM enhances the K48/K63-linked ubiquitylation on c-Jun, thereby enhancing the rate of its subsequent degradation. Functionally defective Fbw7α mutants prevalent in multiple human cancers are reactivated by BLM. However, BS patient-derived BLM mutants cannot potentiate Fbw7α-dependent c-Jun degradation. The decrease in the levels of c-Jun in cells expressing BLM prevents effective c-Jun binding to 2,584 gene promoters. This causes decreases in the transcript and protein levels of c-Jun targets in BLM-expressing cells, resulting in attenuated c-Jun-dependent effects during neoplastic transformation. Thus, BLM carries out its function as a tumor suppressor by enhancing c-Jun turnover and thereby preventing its activity as a proto-oncogene.",
keywords = "adaptor functions, AP-1 transcription factor, Bloom helicase, c-Jun, c-Jun targets, ChIP-seq, Fbw7α, Fbw7α, mutants, RecQ helicase, SCF complex",
author = "Raina Priyadarshini and Mansoor Hussain and Preeti Attri and Ekjot Kaur and Vivek Tripathi and Swati Priya and Parashar Dhapola and Dhurjhoti Saha and Vinoth Madhavan and Shantanu Chowdhury and Sagar Sengupta",
note = "Funding Information: We acknowledge Ian Hickson, Nathan Ellis, Bohdan Wasylyk, Markus Welcker, Bruce Clurman, Rosa Farras, Masaki Matsumoto, Penengo Lorenza, Akhil Banerjea, Jim Goodrich, and Zihua Gong for plasmids and Jerry Shay, Nathan Ellis, and Bert Vogelstein for cells. S.S. acknowledges National Institute of Immunology core funds, the Department of Biotechnology (DBT) of India ( BT/MED/30/SP11263/2015 ), and the Council of Scientific and Industrial Research (CSIR) of India ( 37[1699]/17/EMR-11 ) for financial assistance. S.C. was supported by a Senior Fellowship of the Wellcome Trust/DBT India Alliance (grant 500127/Z/09/Z ). Funding Information: We acknowledge Ian Hickson, Nathan Ellis, Bohdan Wasylyk, Markus Welcker, Bruce Clurman, Rosa Farras, Masaki Matsumoto, Penengo Lorenza, Akhil Banerjea, Jim Goodrich, and Zihua Gong for plasmids and Jerry Shay, Nathan Ellis, and Bert Vogelstein for cells. S.S. acknowledges National Institute of Immunology core funds, the Department of Biotechnology (DBT) of India (BT/MED/30/SP11263/2015), and the Council of Scientific and Industrial Research (CSIR) of India (37[1699]/17/EMR-11) for financial assistance. S.C. was supported by a Senior Fellowship of the Wellcome Trust/DBT India Alliance (grant 500127/Z/09/Z). Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = jul,
day = "24",
doi = "10.1016/j.celrep.2018.06.101",
language = "English (US)",
volume = "24",
pages = "947--961.e7",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}