NER-factor DDB2 regulates HIF1α and hypoxia-response genes in HNSCC

Bommi, Prashant V.; Chand, Vaibhav; Mukhopadhyay, Nishit K.; Raychaudhuri, Pradip; Bagchi, Srilata

doi:10.1038/s41388-019-1105-y

Cited by 18 publications

(15 citation statements)

References 63 publications

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“…Preclinical models with knockdown of DDB2 showed enhanced angiogenesis and tumor growth. 29 DDB2 expression is downregulated in advanced HNSCCs, and loss of DDB2 expression coincides with reduced survival. This may depend both on angiogenesis/ tumor proliferation and on EMT.…”

Section: Neoangiogenesis and Fibrosis/ Stroma And The Ecm In Hnsccmentioning

confidence: 99%

Further Understanding of the Immune Microenvironment in Head and Neck Squamous Cell Carcinoma: Implications for Prognosis

Denaro

Merlano

Nigro

2021

CMAR

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We aimed to review the literature on the tumor microenvironment as a key player in tumor growth and anti-cancer treatment responses in head and neck cancer. Patients and Methods: We reviewed the recent literature on this topic, using the following research words: "tumor microenvironment" and "head and neck cancer or neoplasm or head and neck squamous cell carcinoma" and "immune cells" and "stromal cells". A search was conducted on the PubMed website and reports from international meetings, presentations and abstracts. Results: The tumor microenvironment is a complex network in which myeloid cells, tumoral cells, growth factors and cytokines are involved in angiogenesis, the extracellular matrix and epithelial-to-mesenchymal transition. Conclusion: Immune resistance and rapid tumor growth depend on immunosuppressive and pro-tumoral environments. Further investigations to classify and adequately treat patients with head and neck cancer are required.

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Section: Neoangiogenesis and Fibrosis/ Stroma And The Ecm In Hnsccmentioning

confidence: 99%

Further Understanding of the Immune Microenvironment in Head and Neck Squamous Cell Carcinoma: Implications for Prognosis

Denaro

Merlano

Nigro

2021

CMAR

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“…Interestingly, DDB2 moonlights as a transcriptional regulator by associating with gene promoters and recruiting different components of the histone code machinery [ 81 – 84 ]. In fact, DDB2 can bind to and cooperate with E2F1 to activate transcription [ 85 , 86 ].…”

Section: The Distinction Between Transcription Factors and Dna Repairmentioning

confidence: 99%

The E2F1 transcription factor and RB tumor suppressor moonlight as DNA repair factors

et al. 2020

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The E2F1 transcription factor and RB tumor suppressor are best known for their roles in regulating the expression of genes important for cell cycle progression but, they also have transcriptionindependent functions that facilitate DNA repair at sites of damage. Depending on the type of DNA damage, E2F1 can recruit either the GCN5 or p300/CBP histone acetyltransferases to deposit different histone acetylation marks in flanking chromatin. At DNA double-strand breaks, E2F1 also recruits RB and the BRG1 ATPase to remodel chromatin and promote loading of the MRE11-RAD50-NBS1 complex. Knock-in mouse models demonstrate important roles for E2F1 post-translational modifications in regulating DNA repair and physiological responses to DNA damage. This review highlights how E2F1 moonlights in DNA repair, thus revealing E2F1 as a versatile protein that recruits many of the same chromatin-modifying enzymes to sites of DNA damage to promote repair that it recruits to gene promoters to regulate transcription.

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“…S6 in the supplemental material) but, rather, function during later phases in the process where nucleosome-released DDB2 is degraded to enable DNA damage handover to drive further steps of GG-NER ( 46 ). We suggest that MEKK1-activated CRL4 does not lead to the degradation of only proteins such as DDB2 and p21, which play multiple roles in the regulation of DNA damage, cell proliferation, and survival ( 47 , 48 ), but also of further proteins that need to be identified in the future.…”

Section: Discussionmentioning

confidence: 95%

MEKK1-Dependent Activation of the CRL4 Complex Is Important for DNA Damage-Induced Degradation of p21 and DDB2 and Cell Survival

Bacher

Stekman

Farah

et al. 2021

Molecular and Cellular Biology

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Cullin-4 ubiquitin ligase (CRL4) complexes are differentially composed and highly dynamic protein assemblies that control many biological processes including the global genome nucleotide excision repair (GG-NER) pathway. Here we identified the kinase mitogen-activated protein kinase kinase kinase 1 (MEKK1) as a novel constitutive interactor of a cytosolic CRL4 complex that disassembles after DNA damage due to the Caspase-mediated cleavage of MEKK1. The kinase activity of MEKK1 was important to trigger auto-ubiquitination of the CRL4 complex by K48- and K63-linked ubiquitin chains. MEKK1 knockdown prohibited DNA damage-induced degradation of the CRL4 component DNA-damage binding protein 2 (DDB2) and the CRL4 substrate p21 and also cell recovery and survival. A ubiquitin replacement strategy revealed a contribution of K63-branched ubiquitin chains for DNA damage-induced DDB2/p21 decay, cell cycle regulation and cell survival. These data might have also implications for cancer, as frequently occurring mutations of MEKK1 might have an impact on genome stability and the therapeutic efficacy of CRL4-dependent immunomodulatory drugs such as thalidomide-derivatives.

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NER-factor DDB2 regulates HIF1α and hypoxia-response genes in HNSCC

Cited by 18 publications

References 63 publications

Further Understanding of the Immune Microenvironment in Head and Neck Squamous Cell Carcinoma: Implications for Prognosis

Further Understanding of the Immune Microenvironment in Head and Neck Squamous Cell Carcinoma: Implications for Prognosis

The E2F1 transcription factor and RB tumor suppressor moonlight as DNA repair factors

MEKK1-Dependent Activation of the CRL4 Complex Is Important for DNA Damage-Induced Degradation of p21 and DDB2 and Cell Survival

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