The PI3K/Akt1 pathway enhances steady-state levels of FANCL

Dao, Kim; Rotelli, Michael D.; Brown, Brieanna; Yates, Jane E.; Rantala, Juha; Tognon, Cristina E.; Tyner, Jeffrey W.; Druker, Brian J.; Bagby, Grover C.

doi:10.1091/mbc.e13-03-0144

Cited by 8 publications

(11 citation statements)

References 47 publications

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“…The expression plasmids of GFP-FANCL harboring the C312,315A or C364,367A mutations were obtained from the plasmid for expressing the wild-type GFP-FANCL provided by Dr. Grover C. Bagby from Oregon Health and Science University 17 by using a GeneArt Site-directed Mutagenesis Kit (Thermo Fisher Scientific, Waltham, MA), following the vendor’s recommended procedures.…”

Section: Methodsmentioning

confidence: 99%

Arsenite Binds to the RING Finger Domain of FANCL E3 Ubiquitin Ligase and Inhibits DNA Interstrand Crosslink Repair

Jiang¹,

Bellani

Li³

et al. 2017

ACS Chem. Biol.

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Human exposure to arsenic in drinking water is known to be associated with the development of bladder, lung, kidney, and skin cancers. The molecular mechanisms underlying the carcinogenic effects of arsenic species remain incompletely understood. DNA interstrand cross-links (ICLs) are among the most cytotoxic type of DNA lesions that block DNA replication and transcription, and these lesions can be induced by endogenous metabolism and by exposure to exogenous agents. Fanconi anemia (FA) is a congenital disorder manifested with elevated sensitivity toward DNA interstrand cross-linking agents, and monoubiquitination of FANCD2 by FANCL is a crucial step in FA-mediated DNA repair. Here, we demonstrated that As3+ could bind to the PHD/RING finger domain of FANCL in vitro and in cells. This binding led to compromised ubiquitination of FANCD2 in cells and diminished recruitment of FANCD2 to chromatin and DNA damage sites induced by 4,5′,8-trimethylpsoralen plus UVA irradiation. Furthermore, clonogenic survival assay results showed that arsenite coexposure rendered cells more sensitive toward DNA interstrand cross-linking agents. Together, our study suggested that arsenite may compromise genomic stability via perturbation of the Fanconi anemia pathway, thereby conferring its carcinogenic effect.

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Section: Methodsmentioning

confidence: 99%

Arsenite Binds to the RING Finger Domain of FANCL E3 Ubiquitin Ligase and Inhibits DNA Interstrand Crosslink Repair

Jiang¹,

Bellani

Li³

et al. 2017

ACS Chem. Biol.

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“…We used CacoBBe cells with stable knockdown of occludin (shOcln) generated by Buschmann and colleagues. 15 These occludin knockdown cells were recently reported to provide (i) a >90% reduction in global occludin protein expression, (ii) a reduced TER, and (iii) to have an activated leak pathway, i.e. increased passage of dextrans in the range of 3-40 kDa.…”

Section: Characterization Of Cacobbe Cells With Stable Knockdown Of Omentioning

confidence: 99%

“…However, contrary to the aforementioned studyclaudin-2 expression was found to be reduced in these cells. 15 Though Yu et al and VanItallie et al found no correlation between occludin deficiency and basal flux of macromolecular tracers in MDCK cells they reported a different response to cytokines or to cell physiology-affecting reagents that scale in line with the occludin level in these cells. 11,13 Similar findings were reported in mice showing that cytokine-induced barrier defects depend on occludin.…”

Section: Introductionmentioning

confidence: 95%

“…3,[6][7][8] It has been a long-standing issue to get behind the cellular and molecular mechanisms of the leak pathway with occludin, as one of the tight junction proteins, being suggested to regulate it. [9][10][11][12][13][14][15] Partly on this account, occludin is considered a key marker of epithelial barrier function. associated with many other aspects of epithelial physiology: recent studies related occludin mutations to brain calcification and renal dysfunction.…”

Section: Introductionmentioning

confidence: 99%

“…35 The same was reported for the abovementioned CacoBBe cells stably transfected with occludin-targeting shRNA. 15 This suggested that occludin is involved in the response of the epithelial barrier to perturbations rather than in regulating basal flux.…”

Section: Introductionmentioning

confidence: 99%

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Occludin knockdown is not sufficient to induce transepithelial macromolecule passage

et al. 2019

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Reiche (2019) Occludin knockdown is not sufficient to induce transepithelial macromolecule passage, Tissue Barriers, 7:2, 1612661, ABSTRACT Occludin, a tight junction protein, has been reported to regulate barrier functionparticularly the leak pathway for larger solutesin epithelia. Therefore, we aimed to precisely define its role in macromolecule passage at single cell-cell junctions. A combination of varying occludin expression by transient and stable knockdown including systematic seeding strategies was employed to achieve a broad and defined pattern of variance in occludin expression over epithelia. This variance model enabled us to examine occludin function in the leak pathway using global and local analysis, i.e. to analyze macromolecule flux across epithelia and macromolecule passage at single-cell level. Macromolecular flux was found not to correlate with occludin expression in intestinal epithelial cells. In fact, by spatially resolving macromolecular permeation sites using a recently developed method we uncovered leaky cell junctions at the edge of Transwells resulting in increased passage. This demonstrates that rare leaks can determine net flux of macromolecules across epithelia while the vast majority of cellular junctions do not contribute significantly. Hence, concomitant local analysis of macromolecule passage across epithelial barriers is indispensable for interpretation of global flux data. By combining this new approach with cell culture models of the leak pathway, we can present evidence that lack of occludin is not sufficient to stimulate the epithelial leak pathway. ARTICLE HISTORY

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Fanconi anemia: current insights regarding epidemiology, cancer, and DNA repair

Peake

Noguchi

2022

Hum Genet

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The PI3K/Akt1 pathway enhances steady-state levels of FANCL

Cited by 8 publications

References 47 publications

Arsenite Binds to the RING Finger Domain of FANCL E3 Ubiquitin Ligase and Inhibits DNA Interstrand Crosslink Repair

Arsenite Binds to the RING Finger Domain of FANCL E3 Ubiquitin Ligase and Inhibits DNA Interstrand Crosslink Repair

Occludin knockdown is not sufficient to induce transepithelial macromolecule passage

Fanconi anemia: current insights regarding epidemiology, cancer, and DNA repair

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