Creatine kinase brain-type regulates BCAR1 phosphorylation to facilitate DNA damage repair

Yang, Bo; Zhang, Wentao; Sun, Le; Lü, Bin; Yin, Changsong; Zhang, Yaoyang; Jiang, Hong

doi:10.1016/j.isci.2023.106684

Cited by 3 publications

(1 citation statement)

References 51 publications

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“…RBBP4/7, as subunits of the NuRD complex, mediate the interaction of NuRD with histone tails and transcription factors ( 59 ). Yang et al ( 60 ) showed that breast cancer (BC) anti-estrogen resistance 1 and RBBP4 can form a complex, be recruited to chromatin, and jointly occupy the promoter regions of some DNA repair genes, and promote DNA damage repair. Similarly, RBBP4/7 specifically interact with the C-terminal domain of BC type 1 susceptibility protein (BRCA1) and inhibit its transactivation activity ( 61 ).…”

Section: The Biological Functions Of Rbbp4/7mentioning

confidence: 99%

Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review)

Zhan,

Yin,

et al. 2024

Int J Mol Med

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Histone chaperones serve a pivotal role in maintaining human physiological processes. They interact with histones in a stable manner, ensuring the accurate and efficient execution of DNA replication, repair and transcription. Retinoblastoma binding protein (RBBP)4 and RBBP7 represent a crucial pair of histone chaperones, which not only govern the molecular behavior of histones H3 and H4, but also participate in the functions of several protein complexes, such as polycomb repressive complex 2 and nucleosome remodeling and deacetylase, thereby regulating the cell cycle, histone modifications, DNA damage and cell fate. A strong association has been indicated between RBBP4/7 and some major human diseases, such as cancer, age-related memory loss and infectious diseases. The present review assesses the molecular mechanisms of RBBP4/7 in regulating cellular biological processes, and focuses on the variations in RBBP4/7 expression and their potential mechanisms in various human diseases, thus providing new insights for their diagnosis and treatment.

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Section: The Biological Functions Of Rbbp4/7mentioning

confidence: 99%

Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review)

Zhan,

Yin,

et al. 2024

Int J Mol Med

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CKB Promotes Mitochondrial ATP Production by Suppressing Permeability Transition Pore

He,

Lin,

et al. 2024

Advanced Science

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Creatine kinases are essential for maintaining cellular energy balance by facilitating the reversible transfer of a phosphoryl group from ATP to creatine, however, their role in mitochondrial ATP production remains unknown. This study shows creatine kinases, including CKMT1A, CKMT1B, and CKB, are highly expressed in cells relying on the mitochondrial F1F0 ATP synthase for survival. Interestingly, silencing CKB, but not CKMT1A or CKMT1B, leads to a loss of sensitivity to the inhibition of F1F0 ATP synthase in these cells. Mechanistically, CKB promotes mitochondrial ATP but reduces glycolytic ATP production by suppressing mitochondrial calcium (mCa2+) levels, thereby preventing the activation of mitochondrial permeability transition pore (mPTP) and ensuring efficient mitochondrial ATP generation. Further, CKB achieves this regulation by suppressing mCa2+ levels through the inhibition of AKT activity. Notably, the CKB‐AKT signaling axis boosts mitochondrial ATP production in cancer cells growing in a mouse tumor model. Moreover, this study also uncovers a decline in CKB expression in peripheral blood mononuclear cells with aging, accompanied by an increase in AKT signaling in these cells. These findings thus shed light on a novel signaling pathway involving CKB that directly regulates mitochondrial ATP production, potentially playing a role in both pathological and physiological conditions.

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RBBP4: A novel diagnostic and prognostic biomarker for non‐small‐cell lung cancer correlated with autophagic cell death

Zhan,

Zhang,

Yin

et al. 2024

Cancer Medicine

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BackgroundNon‐small‐cell lung cancer (NSCLC) often presents at later stages, typically associated with poor prognosis. Autophagy genes play a role in the progression of tumors. This study investigated the clinical relevance, prognostic value, and biological significance of RBBP4 in NSCLC.MethodsWe assessed RBBP4 expression using the GSE30219 and TCGA NSCLC datasets and NSCLC cells, exploring its links with clinical outcomes, tumor immunity, and autophagy genes through bioinformatics analysis after transcriptome sequencing of RBBP4‐knockdown and control PC9 cells. We identified differentially expressed genes (DEGs) and conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein–protein interaction network analyses. The significance of autophagy‐related DEGs was evaluated for diagnosis and prognosis using the GSE30219 dataset. Experiments both in vivo and in vitro explored the biological mechanisms behind RBBP4‐mediated autophagic cell death in NSCLC.ResultsRBBP4 overexpression in NSCLC correlates with a poorer prognosis. Eighteen types of immune cell were significantly enriched in cultures that had low RBBP4 expression compared high expression. DEGs associated with RBBP4 are enriched in autophagy pathways. Transcriptomic profiling of the PC9 cell line identified autophagy‐related DEGs associated with RBBP4 that exhibited differential expression in NSCLC, suggesting prognostic applications. In vitro experiments demonstrated that RBBP4 knockdown induced autophagy and apoptosis in PC9 cells, promoting cell death, which was inhibited by 3‐MA. In vivo, targeted siRNA against RBBP4 significantly reduced tumor development in PC9 cell‐injected nude mice, elevating autophagy‐related protein levels and inducing apoptosis and necrosis in tumor tissues.ConclusionIn NSCLC, RBBP4 upregulation correlates with poor prognosis and altered immunity. Its knockdown induces autophagic cell death in NSCLC cells. These results indicate RBBP4 as a potential NSCLC diagnostic marker and its autophagy modulation as a prospective therapeutic target.

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Creatine kinase brain-type regulates BCAR1 phosphorylation to facilitate DNA damage repair

Cited by 3 publications

References 51 publications

Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review)

Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review)

CKB Promotes Mitochondrial ATP Production by Suppressing Permeability Transition Pore

RBBP4: A novel diagnostic and prognostic biomarker for non‐small‐cell lung cancer correlated with autophagic cell death

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