Cell density‐dependent acetylation of ΔNp63α is associated with p53‐dependent cell cycle arrest

Chae, Yang Seok; Kim, Hyunji; Kim, Dongsung; Lee, Hyun‐Sook; Lee, Hae Ock

doi:10.1016/j.febslet.2012.03.021

Cited by 9 publications

(8 citation statements)

References 38 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Then, we performed immunoprecipitation of endogenous ΔNp63 α from total protein extracts of HaCaT cells treated with TSA. The level of ΔNp63 α acetylation was detected using an antibody against acetylated lysines: we observed that ΔNp63 α is found acetylated at a basal level, as previously reported ( 39 ), and that its acetylation increased upon TSA treatment (Fig. 1 B).…”

Section: Resultssupporting

confidence: 87%

FGF8, c-Abl and p300 participate in a pathway that controls stability and function of the ΔNp63αprotein

et al. 2015

View full text Add to dashboard Cite

The p63 transcription factor, homolog to the p53 tumor suppressor gene, plays a crucial role in epidermal and limb development, as its mutations are associated to human congenital syndromes characterized by skin, craniofacial and limb defects. While limb and skin-specific p63 transcriptional targets are being discovered, little is known of the post-translation modifications controlling ΔNp63α functions. Here we show that the p300 acetyl-transferase physically interacts in vivo with ΔNp63α and catalyzes its acetylation on lysine 193 (K193) inducing ΔNp63α stabilization and activating specific transcriptional functions. Furthermore we show that Fibroblast Growth Factor-8 (FGF8), a morphogenetic signaling molecule essential for embryonic limb development, increases the binding of ΔNp63α to the tyrosine kinase c-Abl as well as the levels of ΔNp63α acetylation. Notably, the natural mutant ΔNp63α-K193E, associated to the Split-Hand/Foot Malformation-IV syndrome, cannot be acetylated by this pathway. This mutant ΔNp63α protein displays promoter-specific loss of DNA binding activity and consequent altered expression of development-associated ΔNp63α target genes. Our results link FGF8, c-Abl and p300 in a regulatory pathway that controls ΔNp63α protein stability and transcriptional activity. Hence, limb malformation-causing p63 mutations, such as the K193E mutation, are likely to result in aberrant limb development via the combined action of altered protein stability and altered promoter occupancy.

show abstract

Section: Resultssupporting

confidence: 87%

FGF8, c-Abl and p300 participate in a pathway that controls stability and function of the ΔNp63αprotein

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Besides, two RNA binding proteins, such as PCB1 and HuR, regulate p63 variants at mRNA level (Cho et al, 2013. Phosphorylation and sumoylation of p63 may induce both p63 activation and/or degradation (Chae et al, 2012). Ubiquitin E3 ligases, kinases, and other interactors regulate p63 stability .…”

Section: P63: Regulationmentioning

confidence: 99%

P63 in health and cancer

Gonfloni

Caputo²,

Iannizzotto³

2015

Int. J. Dev. Biol.

View full text Add to dashboard Cite

TP63 is the most ancient member of the p53 gene family. The p53 family comprises three transcription factors (p53/p63/p73). They share a high degree of homology and similar domain structure. Yet, they can exist as truncated isoforms. Alternative promoters and splicing sites lead to the generation of several molecules. P53/p63/p73 are important to maintain cell homeostasis. P63 and p73 regulate many p53 target genes. This is due to their common structural features. Both proteins may compensate the loss of p53. This is a common event occurring in more than 50% of malignancies. Yet, p63 (or p73) has its own role. Studies from p63-null mice have shown the key role of p63 in embryo development. Several reports have supported the p63 role in epidermal development and in skin homeostasis. P63 involvement in heart development is currently being researched. Recent studies have found p63 to be "the guardian of human reproduction". In addition, p63 has an important, even controversial, role in cancer. Here, we provide a general overview of p63 regulation and activity. We discuss emerging concepts about its role in germ line protection, metabolism and cancer.

show abstract

“…Also, the hinge region of ΔNp63α can be acetylated by PCAF in response to high cellular density. PCAF-mediated acetylation of ΔNp63α resulted in its cytoplasmic sequestration and cell cycle arrest [99]. …”

Section: Introductionmentioning

confidence: 99%

Lysine-specific modifications of p53: a matter of life and death?

et al. 2013

View full text Add to dashboard Cite

Post-translational modifications provide a fine-tuned control of protein function(s) in the cell. The well-known tumour suppressor p53 is subject to many post-translational modifications, which alter its activity, localization and stability, thus ultimately modulating its response to various forms of genotoxic stress. In this review, we focus on the role of recently discovered lysine-specific modifications of p53, methylation and acetylation in particular, and their effects on p53 activity in damaged cells. We also discuss a possibility of mutual influence of covalent modifications in the p53 and histone proteins located in the vicinity of p53 binding sites in chromatin and propose important ramifications stemming from this hypothesis.

show abstract

Cell density‐dependent acetylation of ΔNp63α is associated with p53‐dependent cell cycle arrest

Abstract: ΔNp63α physically interacts with p53 by anti bait coimmunoprecipitation ( View interaction )

Cited by 9 publications

References 38 publications

FGF8, c-Abl and p300 participate in a pathway that controls stability and function of the ΔNp63αprotein

FGF8, c-Abl and p300 participate in a pathway that controls stability and function of the ΔNp63αprotein

P63 in health and cancer

Lysine-specific modifications of p53: a matter of life and death?

Contact Info

Product

Resources

About