HMGB1 Protein Interactions in Prostate and Ovary Cancer Models Reveal Links to RNA Processing and Ribosome Biogenesis through NuRD, THOC and Septin Complexes.
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ICR Authors
Authors
Barreiro-Alonso, A
Lamas-Maceiras, M
Lorenzo-Catoira, L
Pardo, M
Yu, L
Choudhary, JS
Cerdán, ME
Lamas-Maceiras, M
Lorenzo-Catoira, L
Pardo, M
Yu, L
Choudhary, JS
Cerdán, ME
Document Type
Journal Article
Date
2021-09-18
Date Accepted
2021-09-14
Abstract
This study reports the HMGB1 interactomes in prostate and ovary cancer cells lines. Affinity purification coupled to mass spectrometry confirmed that the HMGB1 nuclear interactome is involved in HMGB1 known functions such as maintenance of chromatin stability and regulation of transcription, and also in not as yet reported processes such as mRNA and rRNA processing. We have identified an interaction between HMGB1 and the NuRD complex and validated this by yeast-two-hybrid, confirming that the RBBP7 subunit directly interacts with HMGB1. In addition, we describe for the first time an interaction between two HMGB1 interacting complexes, the septin and THOC complexes, as well as an interaction of these two complexes with Rab11. Analysis of Pan-Cancer Atlas public data indicated that several genes encoding HMGB1-interacting proteins identified in this study are dysregulated in tumours from patients diagnosed with ovary and prostate carcinomas. In PC-3 cells, silencing of HMGB1 leads to downregulation of the expression of key regulators of ribosome biogenesis and RNA processing, namely BOP1, RSS1, UBF1, KRR1 and LYAR. Upregulation of these genes in prostate adenocarcinomas is correlated with worse prognosis, reinforcing their functional significance in cancer progression.
Citation
Cancers, 2021, 13 (18), pp. 4686 -
Source Title
Cancers
Publisher
MDPI
ISSN
2072-6694
eISSN
2072-6694
2072-6694
2072-6694
Collections
Research Team
Functional Proteomics
Prote & Metabolomics Fac
Prote & Metabolomics Fac