Advances on the role of the deleted in breast cancer (DBC1) in cancer and autoimmune diseases

Fang, Qiannan; Bellanti, Joseph A.; Zheng, Song Guo

doi:10.1002/jlb.6mr0320-086r

Cited by 8 publications

(10 citation statements)

References 80 publications

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“…A mutation at the phosphorylation site Thr454 of DBC1 also downregulated the signals related to the epithelial-mesenchymal transition (EMT) [ 104 ]. DBC1 is a crucial endogenic inhibitor of SIRT1, which has been implicated in cancer progression and deacetylates p53, leading to a downregulation of its transcriptional activity and thereby to an enhancement of cell proliferation [ 105 ]. CK2-mediated phosphorylation increases the ability of SIRT1 to deacetylate p53 and protect cells from apoptosis after DNA damage [ 106 ].…”

Section: Importance Of Ck2 In Different Hallmarks Of Cancermentioning

confidence: 99%

CK2 and the Hallmarks of Cancer

Firnau

Brieger

2022

Biomedicines

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Cancer is a leading cause of death worldwide. Casein kinase 2 (CK2) is commonly dysregulated in cancer, impacting diverse molecular pathways. CK2 is a highly conserved serine/threonine kinase, constitutively active and ubiquitously expressed in eukaryotes. With over 500 known substrates and being estimated to be responsible for up to 10% of the human phosphoproteome, it is of significant importance. A broad spectrum of diverse types of cancer cells has been already shown to rely on disturbed CK2 levels for their survival. The hallmarks of cancer provide a rationale for understanding cancer’s common traits. They constitute the maintenance of proliferative signaling, evasion of growth suppressors, resisting cell death, enabling of replicative immortality, induction of angiogenesis, the activation of invasion and metastasis, as well as avoidance of immune destruction and dysregulation of cellular energetics. In this work, we have compiled evidence from the literature suggesting that CK2 modulates all hallmarks of cancer, thereby promoting oncogenesis and operating as a cancer driver by creating a cellular environment favorable to neoplasia.

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Section: Importance Of Ck2 In Different Hallmarks Of Cancermentioning

confidence: 99%

CK2 and the Hallmarks of Cancer

Firnau

Brieger

2022

Biomedicines

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“…3 A ). The presence of multiple domains may allow CCAR2 to perform its diverse biological processes such as apoptosis, DNA repair, transcription, metabolism, circadian cycle, and B cell development ( 30 – 34 ).…”

Section: Resultsmentioning

confidence: 99%

“…CCAR2 affects diverse biological processes such as transcription, RNA splicing, circadian rhythm, metabolism, apoptosis, and B-cell development ( 30 – 34 ). The well-studied role of CCAR2 related to tumorigenesis is in apoptosis.…”

mentioning

confidence: 99%

CCAR2 functions downstream of the Shieldin complex to promote double-strand break end-joining

Iyer

Harada

Clairmont

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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The 53BP1-RIF1 pathway restricts the resection of DNA double-strand breaks (DSBs) and promotes blunt end-ligation by non-homologous end joining (NHEJ) repair. The Shieldin complex is a downstream effector of the 53BP1-RIF1 pathway. Here, we identify a component of this pathway, CCAR2/DBC1, which is also required for restriction of DNA end-resection. CCAR2 co-immunoprecipitates with the Shieldin complex, and knockout of CCAR2 in a BRCA1-deficient cell line results in elevated DSB end-resection, RAD51 loading, and PARP inhibitor (PARPi) resistance. Knockout of CCAR2 is epistatic with knockout of other Shieldin proteins. The S1-like RNA-binding domain of CCAR2 is required for its interaction with the Shieldin complex and for suppression of DSB end-resection. CCAR2 functions downstream of the Shieldin complex, and CCAR2 knockout cells have delayed resolution of Shieldin complex foci. Forkhead-associated (FHA)-dependent targeting of CCAR2 to DSB sites re-sensitized BRCA1−/−SHLD2−/− cells to PARPi. Taken together, CCAR2 is a functional component of the 53BP1-RIF1 pathway, promotes the refill of resected DSBs, and suppresses homologous recombination.

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“…As metabolic changes in cells have been identified as novel markers of cancer, DBC1 may play a role in the energy metabolism associated with cancer. 52 Pangon et al 53 showed that, in colon cancer cells, the interaction of MCC and DBC1 in the cytoplasm abolished the inhibitory effect of DBC1 on SIRT1, reduced the acetylation of β-catenin, and inhibited its transcriptional activity. Studies have also shown that DBC1 also binds and inhibits poly(ADP) ribose polymerase (PARP1), a protein that plays a key role in various DNA repair pathways.…”

Section: Papermentioning

confidence: 99%