RNA Stability of the <i>E2A</i>-Encoded Transcription Factor E47 Is Lower in Splenic Activated B Cells from Aged Mice

Frasca, Daniela; Put, Elaine Van der; Landin, Ana Marie; Gong, Dapeng; Riley, Richard L.; Blomberg, Bonnie B.

doi:10.4049/jimmunol.175.10.6633

Cited by 35 publications

(47 citation statements)

References 77 publications

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“…All the experiments herein have been done with females. Our previous studies (Frasca et al, 2005) indicated no significant differences between females and males with regard to aging defects.…”

Section: Micementioning

confidence: 75%

Aging murine B cells have decreased class switch induced by anti-CD40 or BAFF

Frasca

Riley

Blomberg

2007

Experimental Gerontology

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Section: Micementioning

confidence: 75%

Aging murine B cells have decreased class switch induced by anti-CD40 or BAFF

Frasca

Riley

Blomberg

2007

Experimental Gerontology

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“…These eight Ct differences were used to normalize the targeted genes. Thus, though RNA degradation is a characteristic of aged spleen RNA which is more sensitive than the young one to degradation (Frasca et al 2005) it could be normalized by the use of the multiple housekeeping genes. No Ct difference was found in total RNA from livers obtained from young and old rats.…”

Section: Mcrc Proteinsmentioning

confidence: 99%

Aging is an organ-specific process: changes in homeostasis of iron and redox proteins in the rat

Bulvik

Berenshtein

Konijn

et al. 2011

AGE

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Organ-specific changes of iron-and redoxrelated proteins occur with age in the rat. Ferritin, the major iron storage and detoxifying protein, as well as the proteins of the methionine-centered redox cycle (MCRC) were examined in old and young animals, and showed organ-dependent changes. In spleens and livers of aged rats, ferritin (protein) levels were greater than in young ones, and their iron saturation increased, rendering higher ferritin-bound iron (FtBI). Iron saturation of the ferritin molecule in the tongues and sternohyoids of old rats was lower but ferritin level was higher than in young rats, resulting in increased FtBI with age. Ferritin level in the esophagus of older rats was lower than in young rats but its molecular iron content higher thus the total FtBI remained the same. In the larynx, both ferritin and its iron content were the same in young and old animals. MCRC proteins were measured in livers and spleens only. With aging, methionine sulfoxide reductase A and B (MsrA and MsrB) levels in livers and spleens decreased. Thioredoxin1 (Trx) and Trx-reductase1 were elevated in old spleens, but reduced in livers. Aged spleens showed reduced Msr isozyme activity; but in the liver, its activity increased. mRNA changes with age were monitored and found to be organ specific. These organ-specific changes could reflect the different challenges and the selective pathways of each organ and its resultant capacity to cope with aging.

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“…We have previously shown that, in senescence, posttranscriptional mechanisms in B cell precursors generate reduced E47 protein expression (12); however, in activated splenic B cells reduced E47 mRNA stability is responsible for lower levels of E47 protein (13). In a recent report (14), the degradation of E47 proteins in lymphocytes was shown to be promoted by serine/threonine MAPKs and to be highly dependent upon activation of the Notch pathway.…”

mentioning

confidence: 97%

Accelerated Notch-Dependent Degradation of E47 Proteins in Aged B Cell Precursors Is Associated with Increased ERK MAPK Activation

King

Put

Blomberg

et al. 2007

The Journal of Immunology

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The transcriptional regulator E47, encoded by the E2A gene, is crucial to B lymphopoiesis. In BALB/c senescent mice (∼2 years old), the incidence of E47-expressing pro-B cells in vivo and E47 protein steady state levels in B cell precursors in vitro were reduced. Poor expression of E47 protein was a consequence of accelerated proteasome-mediated turnover and was associated with heightened ubiquitin modification of E2A-encoded proteins in aged B cell precursors. Both MAPK and Notch activity have been previously associated with E2A-encoded protein stability in lymphocytes. Aged B cell precursors exhibited heightened levels of MAPK activity reflected in increased levels of phospho-ERK proteins. Phosphorylation of E2A-encoded proteins was also increased in aged B cell precursors and pharmacologic inhibition of MEK-1 resulted in a partial restoration of their E47 protein. Both Notch proteins and their Delta-like ligands were detected comparably in young and aged B cell precursors. Either inhibition of Notch activation via gamma-secretase or Ab blockade of Notch-Delta-like ligand interactions partially restored E47 expression in aged B cell precursors. We hypothesize that increased MAPK activity promotes phosphorylation of E2A-encoded protein in aged B cell precursors. Subsequently, E2A-encoded proteins undergo ubiquitination and accelerated degradation in a Notch-dependent process. The dysregulation of E2A-encoded protein expression may contribute to the reductions seen in early B lymphopoiesis during murine senescence.

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RNA Stability of the E2A-Encoded Transcription Factor E47 Is Lower in Splenic Activated B Cells from Aged Mice

Cited by 35 publications

References 77 publications

Aging murine B cells have decreased class switch induced by anti-CD40 or BAFF

Aging murine B cells have decreased class switch induced by anti-CD40 or BAFF

Aging is an organ-specific process: changes in homeostasis of iron and redox proteins in the rat

Accelerated Notch-Dependent Degradation of E47 Proteins in Aged B Cell Precursors Is Associated with Increased ERK MAPK Activation

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