HMGB1 Protein Interactions in Prostate and Ovary Cancer Models Reveal Links to RNA Processing and Ribosome Biogenesis through NuRD, THOC and Septin Complexes

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 als...

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Bibliographic Details
Published in:Cancers 2021-09, Vol.13 (18), p.4686
Main Authors: Barreiro-Alonso, Aida, Lamas-Maceiras, Mónica, Lorenzo-Catoira, Lidia, Pardo, Mercedes, Yu, Lu, Choudhary, Jyoti S., Cerdán, M. Esperanza
Format: Article
Language:English
Subjects:
Antibodies
Biosynthesis
Cell growth
Chromatin
Fractionation
Gene expression
Gene regulation
Histone deacetylase
HMGB1 protein
Localization
Mass spectrometry
Mass spectroscopy
NuRD protein
Ovarian cancer
Ovarian carcinoma
Overexpression
Peptides
Phosphatase
Prostate
Prostate cancer
Prostate carcinoma
Protein interaction
Proteins
Proteomics
RNA processing
rRNA
Scientific imaging
Septin
Transcription
Transcription factors
Tumors
Yeast
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13184686