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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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/18/4686 |
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| author | Aida Barreiro-Alonso Mónica Lamas-Maceiras Lidia Lorenzo-Catoira Mercedes Pardo Lu Yu Jyoti S. Choudhary M. Esperanza Cerdán |
| author_facet | Aida Barreiro-Alonso Mónica Lamas-Maceiras Lidia Lorenzo-Catoira Mercedes Pardo Lu Yu Jyoti S. Choudhary M. Esperanza Cerdán |
| author_sort | Aida Barreiro-Alonso |
| collection | DOAJ |
| description | 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 <i>HMGB1</i> leads to downregulation of the expression of key regulators of ribosome biogenesis and RNA processing, namely <i>BOP1</i>, <i>RSS1</i>, <i>UBF1</i>, <i>KRR1</i> and <i>LYAR</i>. Upregulation of these genes in prostate adenocarcinomas is correlated with worse prognosis, reinforcing their functional significance in cancer progression. |
| first_indexed | 2024-03-10T07:50:15Z |
| format | Article |
| id | doaj.art-565ac05a8b744477b05357fbf5382949 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T07:50:15Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-565ac05a8b744477b05357fbf53829492023-11-22T12:19:03ZengMDPI AGCancers2072-66942021-09-011318468610.3390/cancers13184686HMGB1 Protein Interactions in Prostate and Ovary Cancer Models Reveal Links to RNA Processing and Ribosome Biogenesis through NuRD, THOC and Septin ComplexesAida Barreiro-Alonso0Mónica Lamas-Maceiras1Lidia Lorenzo-Catoira2Mercedes Pardo3Lu Yu4Jyoti S. Choudhary5M. Esperanza Cerdán6EXPRELA Group, Centro de Investigaciones Científicas Avanzadas (CICA), University of A Coruña (UDC), 15008 A Coruña, SpainEXPRELA Group, Centro de Investigaciones Científicas Avanzadas (CICA), University of A Coruña (UDC), 15008 A Coruña, SpainEXPRELA Group, Centro de Investigaciones Científicas Avanzadas (CICA), University of A Coruña (UDC), 15008 A Coruña, SpainFunctional Proteomics, The Institute of Cancer Research, London SW7 3RP, UKFunctional Proteomics, The Institute of Cancer Research, London SW7 3RP, UKFunctional Proteomics, The Institute of Cancer Research, London SW7 3RP, UKEXPRELA Group, Centro de Investigaciones Científicas Avanzadas (CICA), University of A Coruña (UDC), 15008 A Coruña, SpainThis 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 <i>HMGB1</i> leads to downregulation of the expression of key regulators of ribosome biogenesis and RNA processing, namely <i>BOP1</i>, <i>RSS1</i>, <i>UBF1</i>, <i>KRR1</i> and <i>LYAR</i>. Upregulation of these genes in prostate adenocarcinomas is correlated with worse prognosis, reinforcing their functional significance in cancer progression.https://www.mdpi.com/2072-6694/13/18/4686HMGB1 interactomeribosome biogenesisRNA processingovary cancerprostate cancer |
| spellingShingle | Aida Barreiro-Alonso Mónica Lamas-Maceiras Lidia Lorenzo-Catoira Mercedes Pardo Lu Yu Jyoti S. Choudhary M. Esperanza Cerdán HMGB1 Protein Interactions in Prostate and Ovary Cancer Models Reveal Links to RNA Processing and Ribosome Biogenesis through NuRD, THOC and Septin Complexes Cancers HMGB1 interactome ribosome biogenesis RNA processing ovary cancer prostate cancer |
| title | HMGB1 Protein Interactions in Prostate and Ovary Cancer Models Reveal Links to RNA Processing and Ribosome Biogenesis through NuRD, THOC and Septin Complexes |
| title_full | HMGB1 Protein Interactions in Prostate and Ovary Cancer Models Reveal Links to RNA Processing and Ribosome Biogenesis through NuRD, THOC and Septin Complexes |
| title_fullStr | HMGB1 Protein Interactions in Prostate and Ovary Cancer Models Reveal Links to RNA Processing and Ribosome Biogenesis through NuRD, THOC and Septin Complexes |
| title_full_unstemmed | HMGB1 Protein Interactions in Prostate and Ovary Cancer Models Reveal Links to RNA Processing and Ribosome Biogenesis through NuRD, THOC and Septin Complexes |
| title_short | HMGB1 Protein Interactions in Prostate and Ovary Cancer Models Reveal Links to RNA Processing and Ribosome Biogenesis through NuRD, THOC and Septin Complexes |
| title_sort | hmgb1 protein interactions in prostate and ovary cancer models reveal links to rna processing and ribosome biogenesis through nurd thoc and septin complexes |
| topic | HMGB1 interactome ribosome biogenesis RNA processing ovary cancer prostate cancer |
| url | https://www.mdpi.com/2072-6694/13/18/4686 |
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