Post-translational Modifications of the p53 Transcription Factor

2007 ◽  
pp. 257-272
Author(s):  
Christopher L. Brooks ◽  
Wei Gu
Keyword(s):  
Transcription Factor ◽  
Post Translational Modifications

scholarly journals Phosphorylation of the Regulators, a Complex Facet of NF-κB Signaling in Cancer

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 15
Author(s):  
Aishat Motolani ◽  
Matthew Martin ◽  
Mengyao Sun ◽  
Tao Lu
Keyword(s):  
Transcription Factor ◽  
Cardiovascular Diseases ◽  
Cancer Progression ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Malignant Diseases ◽  
Future Perspectives ◽  
Post Translational Modifications ◽  
Site Specific

The nuclear factor kappa B (NF-κB) is a ubiquitous transcription factor central to inflammation and various malignant diseases in humans. The regulation of NF-κB can be influenced by a myriad of post-translational modifications (PTMs), including phosphorylation, one of the most popular PTM formats in NF-κB signaling. The regulation by phosphorylation modification is not limited to NF-κB subunits, but it also encompasses the diverse regulators of NF-κB signaling. The differential site-specific phosphorylation of NF-κB itself or some NF-κB regulators can result in dysregulated NF-κB signaling, often culminating in events that induce cancer progression and other hyper NF-κB related diseases, such as inflammation, cardiovascular diseases, diabetes, as well as neurodegenerative diseases, etc. In this review, we discuss the regulatory role of phosphorylation in NF-κB signaling and the mechanisms through which they aid cancer progression. Additionally, we highlight some of the known and novel NF-κB regulators that are frequently subjected to phosphorylation. Finally, we provide some future perspectives in terms of drug development to target kinases that regulate NF-κB signaling for cancer therapeutic purposes.

scholarly journals Glucose-induced expression of the homeotic transcription factor Prep1 is associated with histone post-translational modifications in skeletal muscle

Diabetologia ◽  
2015 ◽  
Vol 59 (1) ◽  
pp. 176-186 ◽  
Author(s):  
Marco Ciccarelli ◽  
Viviana Vastolo ◽  
Luigi Albano ◽  
Manuela Lecce ◽  
Serena Cabaro ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factor ◽  
Induced Expression ◽  
Post Translational Modifications

scholarly journals Pax8 protein stability is controlled by sumoylation

2008 ◽  
Vol 42 (1) ◽  
pp. 35-46 ◽  
Author(s):  
Tiziana de Cristofaro ◽  
Anna Mascia ◽  
Andrea Pappalardo ◽  
Barbara D'Andrea ◽  
Lucio Nitsch ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Critical Role ◽  
Nuclear Bodies ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Signal Transducers ◽  
Protein Protein Interaction ◽  
Sumo Ligase ◽  
Development And Differentiation ◽  
Substitution Mutant

The transcription factor Pax8 is involved in the morphogenesis of the thyroid gland and in the maintenance of the differentiated thyroid phenotype. Despite the critical role played by Pax8 during thyroid development and differentiation, very little is known of its post-translational modifications and how these modifications may regulate its activity. We focused our attention on the study of a specific post-translational modification, i.e., sumoylation. Sumoylation is a dynamic and reversible process regulating gene expression by altering transcription factor stability, protein–protein interaction and subcellular localization of target proteins. The analysis of Pax8 protein sequence revealed the presence of one sumoylation consensus motif (ψKxE), strongly conserved among mammals, amphibians, and fish. We demonstrated that Pax8 is sumoylated by the addition of a single small ubiquitin-like modifier (SUMO) molecule on its lysine residue 309 and that Pax8K309R, a substitution mutant in which the candidate lysine is replaced with an arginine, is no longer modified by SUMO. In addition, we analyzed whether protein inhibitor of activated signal transducers and activators of transcription (PIASy), a member of the PIAS STAT family of proteins, could function as a SUMO ligase and we demonstrated that indeed PIASy is able to increase the fraction of sumoylated Pax8. Interestingly, we show that Pax8 is targeted in the SUMO nuclear bodies, which are structures that regulate the nucleoplasmic concentration of transcription factors by SUMO trapping. Finally, we report here that the steady-state protein level of Pax8 is controlled by sumoylation.

scholarly journals EGR1 Transcription Factor is a Multifaceted Regulator of Matrix Production in Tendons and Other Connective Tissues

2020 ◽  
Vol 21 (5) ◽  
pp. 1664 ◽  
Author(s):  
Emmanuelle Havis ◽  
Delphine Duprez
Keyword(s):  
Extracellular Matrix ◽  
Transcription Factor ◽  
Connective Tissue ◽  
Transcriptional Activity ◽  
Tendon Repair ◽  
Regulatory Elements ◽  
Biological Functions ◽  
Connective Tissues ◽  
Post Translational Modifications ◽  
Matrix Production

Although the transcription factor EGR1 is known as NGF1-A, TIS8, Krox24, zif/268, and ZENK, it still has many fewer names than biological functions. A broad range of signals induce Egr1 gene expression via numerous regulatory elements identified in the Egr1 promoter. EGR1 is also the target of multiple post-translational modifications, which modulate EGR1 transcriptional activity. Despite the myriad regulators of Egr1 transcription and translation, and the numerous biological functions identified for EGR1, the literature reveals a recurring theme of EGR1 transcriptional activity in connective tissues, regulating genes related to the extracellular matrix. Egr1 is expressed in different connective tissues, such as tendon (a dense connective tissue), cartilage and bone (supportive connective tissues), and adipose tissue (a loose connective tissue). Egr1 is involved in the development, homeostasis, and healing processes of these tissues, mainly via the regulation of extracellular matrix. In addition, Egr1 is often involved in the abnormal production of extracellular matrix in fibrotic conditions, and Egr1 deletion is seen as a target for therapeutic strategies to fight fibrotic conditions. This generic EGR1 function in matrix regulation has little-explored implications but is potentially important for tendon repair.

scholarly journals In Silico Identification of SOX1 Post-Translational Modifications Highlights a Shared Protein Motif

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2471
Author(s):  
Azaz Ahmad ◽  
Stephanie Strohbuecker ◽  
Claudia Scotti ◽  
Cristina Tufarelli ◽  
Virginie Sottile
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Translational Regulation ◽  
Cell Development ◽  
Transcriptional Level ◽  
Protein Motif ◽  
Post Translational Modifications ◽  
Undifferentiated State ◽  
New Research

The transcription factor SOX1 is a key regulator of neural stem cell development, acting to keep neural stem cells (NSCs) in an undifferentiated state. Postnatal expression of Sox1 is typically confined to the central nervous system (CNS), however, its expression in non-neural tissues has recently been implicated in tumorigenesis. The mechanism through which SOX1 may exert its function is not fully understood, and studies have mainly focused on changes in SOX1 expression at a transcriptional level, while its post-translational regulation remains undetermined. To investigate this, data were extracted from different publicly available databases and analysed to search for putative SOX1 post-translational modifications (PTMs). Results were compared to PTMs associated with SOX2 in order to identify potentially key PTM motifs common to these SOXB1 proteins, and mapped on SOX1 domain structural models. This approach identified several putative acetylation, phosphorylation, glycosylation and sumoylation sites within known functional domains of SOX1. In particular, a novel SOXB1 motif (xKSExSxxP) was identified within the SOX1 protein, which was also found in other unrelated proteins, most of which were transcription factors. These results also highlighted potential phospho-sumoyl switches within this SOXB1 motif identified in SOX1, which could regulate its transcriptional activity. This analysis indicates different types of PTMs within SOX1, which may influence its regulatory role as a transcription factor, by bringing changes to its DNA binding capacities and its interactions with partner proteins. These results provide new research avenues for future investigations on the mechanisms regulating SOX1 activity, which could inform its roles in the contexts of neural stem cell development and cancer.

scholarly journals FOXL2: a central transcription factor of the ovary

2013 ◽  
Vol 52 (1) ◽  
pp. R17-R33 ◽  
Author(s):  
Adrien Georges ◽  
Aurelie Auguste ◽  
Laurianne Bessière ◽  
Anne Vanet ◽  
Anne-Laure Todeschini ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Forkhead Transcription Factor ◽  
Gene Encoding ◽  
Post Translational Modifications ◽  
Forkhead Box ◽  
Molecular Aspects ◽  
And Function ◽  
Craniofacial Defects ◽  
The Impact

Forkhead box L2 (FOXL2) is a gene encoding a forkhead transcription factor preferentially expressed in the ovary, the eyelids and the pituitary gland. Its germline mutations are responsible for the blepharophimosis ptosis epicanthus inversus syndrome, which includes eyelid and mild craniofacial defects associated with primary ovarian insufficiency. Recent studies have shown the involvement of FOXL2 in virtually all stages of ovarian development and function, as well as in granulosa cell (GC)-related pathologies. A central role of FOXL2 is the lifetime maintenance of GC identity through the repression of testis-specific genes. Recently, a highly recurrent somatic FOXL2 mutation leading to the p.C134W subtitution has been linked to the development of GC tumours in the adult, which account for up to 5% of ovarian malignancies. In this review, we summarise data on FOXL2 modulators, targets, partners and post-translational modifications. Despite the progresses made thus far, a better understanding of the impact of FOXL2 mutations and of the molecular aspects of its function is required to rationalise its implication in various pathophysiological processes.

scholarly journals Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types

2020 ◽  
Vol 21 (22) ◽  
pp. 8843
Author(s):  
Agnieszka Taracha-Wisniewska ◽  
Grzegorz Kotarba ◽  
Sebastian Dworkin ◽  
Tomasz Wilanowski
Keyword(s):  
Transcription Factor ◽  
Regulation Of Transcription ◽  
Critical Function ◽  
Post Translational Modifications ◽  
Tumor Subtypes ◽  
Protein Levels ◽  
Common Cancer ◽  
Cancer Types ◽  
Cellular Integrity ◽  
Upstream Regulators

Krüppel-like factor 4 (KLF4) is a transcription factor highly conserved in evolution. It is particularly well known for its role in inducing pluripotent stem cells. In addition, KLF4 plays many roles in cancer. The results of most studies suggest that KLF4 is a tumor suppressor. However, the functioning of KLF4 is regulated at many levels. These include regulation of transcription, alternative splicing, miRNA, post-translational modifications, subcellular localization, protein stability and interactions with other molecules. Simple experiments aimed at assaying transcript levels or protein levels fail to address this complexity and thus may deliver misleading results. Tumor subtypes are also important; for example, in prostate cancer KLF4 is highly expressed in indolent tumors where it impedes tumor progression, while it is absent from aggressive prostate tumors. KLF4 is important in regulating response to many known drugs, and it also plays a role in tumor microenvironment. More and more information is available about upstream regulators, downstream targets and signaling pathways associated with the involvement of KLF4 in cancer. Furthermore, KLF4 performs critical function in the overall regulation of tissue homeostasis, cellular integrity, and progression towards malignancy. Here we summarize and analyze the latest findings concerning this fascinating transcription factor.

Innate link between NF-κB activity and ubiquitin-like modifiers

2008 ◽  
Vol 36 (5) ◽  
pp. 853-857 ◽  
Author(s):  
Valérie Lang ◽  
Manuel S. Rodríguez
Keyword(s):  
Transcription Factor ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Post Translational Modifications ◽  
Macromolecular Complexes ◽  
The Status ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Pathway Regulation ◽  
The One

Among the several signalling pathways regulated by ubiquitin and ubiquitin-like proteins, the one activating NF-κB (nuclear factor κB) is certainly one of the best characterized. The regulation of the activity of this transcription factor by members of the ubiquitin family occurs at various levels, imposing overlapping controls of security of intriguing complexity. The formation of active macromolecular complexes such as the IKK [IκB (inhibitory κB) kinase] complex is tightly regulated by these post-translational modifications probably due to the fact that many signals converge on this signal's roundabout. An additional, very important level of NF-κB control occurs through the partial or total proteolysis of precursor and inhibitor molecules exerted by the ubiquitin–proteasome pathway. Regulation at this level implicates various conjugating and de-conjugating activities for ubiquitin, SUMO (small ubiquitin-related modifier) and NEDD8. Here, we summarize some of these events and underline the importance of the interconnecting ubiquitin and ubiquitin-like conjugating pathways that determine the status of the activity of this critical transcription factor.

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