Dataset Information

Global transcriptional coactivators CREB-binding protein and p300 are highly essential collectively but not individually in peripheral B cells.

ABSTRACT: CREB-binding protein (CBP) and its para-log p300 are transcriptional coactivators that physically or functionally interact with over 320 mammalian and viral proteins, including 36 that are essential for B cells in mice. CBP and p300 are generally considered limiting for transcription, yet their roles in adult cell lineages are largely unknown since homozygous null mutations in either gene or compound heterozygosity cause early embryonic lethality in mice. We tested the hypotheses that CBP and p300 are limiting and that each has unique properties in B cells, by using mice with Cre/LoxP conditional knockout alleles for CBP (CBP(flox)) and p300 (p300(flox)), which carry CD19(Cre) that initiates floxed gene recombination at the pro-B-cell stage. CD19(Cre)-mediated loss of CBP or p300 led to surprisingly modest deficits in B-cell numbers, whereas inactivation of both genes was not tolerated by peripheral B cells. There was a moderate decrease in B-cell receptor (BCR)-responsive gene expression in CBP or p300 homozygous null B cells, suggesting that CBP and p300 are essential for this signaling pathway that is crucial for B-cell homeostasis. These results indicate that individually CBP and p300 are partially limiting beyond the pro-B-cell stage and that other coactivators in B cells cannot replace their combined loss.

SUBMITTER: Xu W

PROVIDER: S-EPMC1895794 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature

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Global transcriptional coactivators CREB-binding protein and p300 are highly essential collectively but not individually in peripheral B cells.

Xu Wu W Fukuyama Tomofusa T Ney Paul A PA Wang Demin D Rehg Jerold J Boyd Kelli K van Deursen Jan M A JM Brindle Paul K PK

Blood 20060119 11

CREB-binding protein (CBP) and its para-log p300 are transcriptional coactivators that physically or functionally interact with over 320 mammalian and viral proteins, including 36 that are essential for B cells in mice. CBP and p300 are generally considered limiting for transcription, yet their roles in adult cell lineages are largely unknown since homozygous null mutations in either gene or compound heterozygosity cause early embryonic lethality in mice. We tested the hypotheses that CBP and p3 ...[more]

PMID: 16424387

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Project description:ImportanceOccupational exposure to carcinogens has been shown to pose a serious disease burden at the global, regional, and national levels. Based on epidemiologic studies and clinical observations, working environment appears to have important effects on the occurrence of human malignant tumors; however, to date, no systematic articles have been published that specifically investigated cancer burden due to occupational exposure in an individual and collective manner.ObjectiveTo estimate the degree of exposure and evaluate the cancer burden attributable to occupational carcinogens (OCs) individually and collectively by sex, age, year, and location.Design, setting, and participantsCross-sectional study including data on 195 countries from the Global Burden of Diseases, Injuries, and Risk Factors Study from January 1, 1990, to December 31, 2017. Data were analyzed from June 24, 2020, to July 20, 2020.ExposuresThirteen OCs (ie, arsenic, asbestos, benzene, beryllium, cadmium, chromium, diesel engine exhaust, formaldehyde, nickel, polycyclic aromatic hydrocarbons, silica, sulfuric acid, and trichloroethylene).Main outcomes and measuresThe degree and change patterns of exposure as well as the attributable cancer burden, including deaths and disability-adjusted life years (DALYs), by sex, age, year, and location for 13 OCs. The calculation of the population-attributable fraction was based on past exposure in the population and relative risks.ResultsBased on the GBD 2017 study, 13 OCs attributable to 7 cancer types were included. Most summary exposure values for the 13 OCs, particularly those of diesel engine exhaust (35.6% increase; 95% uncertainty interval [UI], 32.4%-38.5%) and trichloroethylene (30.3% increase; 95% UI, 27.3%-33.5%), increased from 1990 to 2017. Only exposure to asbestos decreased by 13.8% (95% UI, -26.7% to 2.2%). In 2017, 319 000 (95% UI, 256 000-382 000) cancer deaths and 6.42 million (95% UI, 5.15 million to 7.76 million) DALYs were associated with OCs combined, accounting for 61.0% (95% UI, 59.6%-62.4%) of the total cancer deaths and 48.3% (46.3% to 50.2%) of the DALYs. Among the 13 OCs, the 3 leading risk factors for cancer burden were asbestos (71.8%), silica (15.4%), and diesel engine exhaust (5.6%). For most OCs, the attributed cancer outcome was tracheal, bronchial, and lung cancer, which accounted for 89.0% of attributable cancer deaths. China (61 644 cancer deaths), the US (42 848), and Japan (20 748) accounted for the largest number of attributable cancer deaths in 2017; for DALYs, China (1.47 million), the US (0.71 million), and India (0.37 million) were the 3 leading countries.Conclusions and relevanceResults of this study suggest that although OC exposure levels have decreased, the overall cancer burden is continuously increasing.

Dataset Information

Global transcriptional coactivators CREB-binding protein and p300 are highly essential collectively but not individually in peripheral B cells.

Publications

Global transcriptional coactivators CREB-binding protein and p300 are highly essential collectively but not individually in peripheral B cells.

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