Gadd45a Is an RNA Binding Protein and Is Localized in Nuclear Speckles

Sytnikova, Yuliya A.; Kubarenko, Andriy V.; Schäfer, Andrea; Weber, Alexander N.R.; Niehrs, Christof

doi:10.1371/journal.pone.0014500

Cited by 50 publications

(48 citation statements)

References 65 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In non-muscle cells, Gadd45a resides in ribosome-sized particles composed of both protein and RNA (51), and it promotes DNA demethylation by uniting thymine DNA glycosylase and activation-induced deaminase in a multimeric complex (52). In addition, Gadd45a and its paralog Gadd45b can function as transcriptional coactivators (53,54).…”

Section: Discussionmentioning

confidence: 99%

Stress-induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy

Ebert

Dyle

Kunkel

et al. 2012

Journal of Biological Chemistry

187

311

View full text Add to dashboard Cite

Background:In skeletal muscle, diverse stresses induce the transcription factor ATF4, which promotes muscle atrophy by an unknown mechanism. Results: ATF4 causes muscle atrophy by inducing Gadd45a, which reprograms myonuclear gene expression to repress antiatrophy mechanisms and induce pro-atrophy mechanisms. Conclusion: Gadd45a is a critical stress-induced mediator of muscle atrophy. Significance: The ATF4/Gadd45a pathway is a potential therapeutic target in atrophic muscle.

show abstract

Section: Discussionmentioning

confidence: 99%

Stress-induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy

Ebert

Dyle

Kunkel

et al. 2012

Journal of Biological Chemistry

187

311

View full text Add to dashboard Cite

show abstract

“…This domain confers the RNA binding properties and characteristics of a ribonucleoprotein particle to Gadd45 α (Sytnikova et al, 2011). Our analysis using the InParanoid database (Ostlund et al, 2010) showed that Gadd45 orthologs first appeared in mollusks, and was also found in anemones, polychaete worms, insects, fish, amphibians and mammals.…”

Section: Gadd45 Family: Structure Partners and Evolutionary Consmentioning

confidence: 99%

Gadd45 proteins: Relevance to aging, longevity and age-related pathologies

Moskalev

Smit-McBride

Shaposhnikov

et al. 2012

Ageing Research Reviews

127

124

View full text Add to dashboard Cite

The Gadd45 proteins have been intensively studied, in view of their important role in key cellular processes. Indeed, the Gadd45 proteins stand at the crossroad of the cell fates by controlling the balance between cell (DNA) repair, eliminating (apoptosis) or preventing the expansion of potentially dangerous cells (cell cycle arrest, cellular senescence), and maintaining the stem cell pool. However, the biogerontological aspects have not thus far received sufficient attention. Here we analyzed the pathways and modes of action by which Gadd45 members are involved in aging, longevity and age-related diseases. Because of their pleiotropic action, a decreased inducibility of Gadd45 members may have far-reaching consequences including genome instability, accumulation of DNA damage, and disorders in cellular homeostasis – all of which may eventually contribute to the aging process and age-related disorders (promotion of tumorigenesis, immune disorders, insulin resistance and reduced responsiveness to stress). Most recently, the dGadd45 gene has been identified as a longevity regulator in Drosophila. Although further wide-scale research is warranted, it is becoming increasingly clear that Gadd45s are highly relevant to aging, age-related diseases (ARDs) and to the control of life span, suggesting them as potential therapeutic targets in ARDs and pro-longevity interventions.

show abstract

“…In fact, due to the evolutionary conservation of the APOBECs and their expression in many different cell types, it might not be surprising if their epigenetic capability is their truly original activity [41,42,43]; while B cells usurped that property of AID to mediate mutations at the Ig locus of B cells [10]. The role of me C and 5-hydroxymethylcytosine ( hm C) [44,45,46] has been epigenetically implicated in the regulation of histone modifications and of gene expression [47,48]. Recent studies strongly suggest that APOBEC proteins – including AID – have the potential to promote demethylation of me C [38,49,50,51] and hm C [47], which could result in epigenomic remodeling of the cell (Figure 1).…”

Section: Genetic and Epigenetic Consequences Of Enzymatically-mediatementioning

confidence: 99%

Mismatch-mediated error prone repair at the immunoglobulin genes

Chahwan¹,

Edelmann²,

Scharff³

et al. 2011

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

The generation of effective antibodies depends upon somatic hypermutation (SHM) and class-switch recombination (CSR) of antibody genes by activation induced cytidine deaminase (AID) and the subsequent recruitment of error prone base excision and mismatch repair. While AID initiates and is required for SHM, more than half of the base changes that accumulate in V regions are not due to the direct deamination of dC to dU by AID, but rather arise through the recruitment of the mismatch repair complex (MMR) to the U:G mismatch created by AID and the subsequent perversion of mismatch repair from a high fidelity process to one that is very error prone. In addition, the generation of double-strand breaks (DSBs) is essential during CSR, and the resolution of AID-generated mismatches by MMR to promote such DSBs is critical for the efficiency of the process. While a great deal has been learned about how AID and MMR cause hypermutations and DSBs, it is still unclear how the error prone aspect of these processes is largely restricted to antibody genes. The use of knockout models and mice expressing mismatch repair proteins with separation-of-function point mutations have been decisive in gaining a better understanding of the roles of each of the major MMR proteins and providing further insight into how mutation and repair are coordinated. Here, we review the cascade of MMR factors and repair signals that are diverted from their canonical error free role and hijacked by B cells to promote genetic diversification of the Ig locus. This error prone process involves AID as the inducer of enzymatically-mediated DNA mismatches, and a plethora of downstream MMR factors acting as sensors, adaptors and effectors of a complex and tightly regulated process from much of which is not yet well understood.

show abstract

Gadd45a Is an RNA Binding Protein and Is Localized in Nuclear Speckles

Cited by 50 publications

References 65 publications

Stress-induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy

Stress-induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy

Gadd45 proteins: Relevance to aging, longevity and age-related pathologies

Mismatch-mediated error prone repair at the immunoglobulin genes

Contact Info

Product

Resources

About