Regulation of p63 Protein Stability via Ubiquitin-Proteasome Pathway

Li, Chenghua; Xiao, Zhi‐Xiong Jim

doi:10.1155/2014/175721

Cited by 26 publications

(30 citation statements)

References 68 publications

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“…In addition, dramatic reduction in p63 levels that follows PKD3 silencing suggests that a role for PKD3 signaling in p63 stabilization. Because of key roles of p63 in cell growth and proliferation, apoptosis and differentiation, p63 levels are tightly regulated, mainly by the ubiquitin-dependent proteasomal degradation pathway (38). Recent studies have shown that degradation of p63 during KC differentiation by E3 ubiquitin ligase requires GSK3 kinase activity (39).…”

Section: Discussionmentioning

confidence: 99%

Opposing Growth Regulatory Roles of Protein Kinase D Isoforms in Human Keratinocytes

Ryvkin

Rashel

Gaddapara

et al. 2015

Journal of Biological Chemistry

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Background:The role of protein kinase D (PKD) signaling in human epidermis is unclear. Results: PKD isoforms have distinct and opposing growth regulatory functions in human keratinocytes. PKD3 is down-regulated upon differentiation and PKD3 silencing results in loss of keratinocyte proliferative potential. Conclusion: PKD signaling is essential for maintaining human epidermal homeostasis. Significance: PKD3 represents a potential drug target in hyperproliferative skin disorders.

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Section: Discussionmentioning

confidence: 99%

Opposing Growth Regulatory Roles of Protein Kinase D Isoforms in Human Keratinocytes

Ryvkin

Rashel

Gaddapara

et al. 2015

Journal of Biological Chemistry

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“…). Mutations in the TP63 gene have been associated with human developmental diseases and skin abnormalities (Li & Xiao , Soares & Zhou ), as well as with different cancer types, such as lung, breast, bladder and squamous cell carcinoma (Hu et al . , Zhang et al .…”

Section: Introductionmentioning

confidence: 99%

Potential role of TP63 in apical periodontitis development

et al. 2019

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Aim To investigate the expression of TP63 in apical periodontitis (AP) tissues and the association of single nucleotide polymorphisms (SNPs) in the TP63 gene with AP using a case‐control dataset. Methodology Expression of TP63 in human AP lesions (apical abscess, radicular cyst, periapical granuloma) was evaluated using immunohistochemistry. A case‐control association study was performed to assess the association of TP63 polymorphisms in individuals having AP with or without associated pain. Cases were defined as subjects with deep caries and AP (n = 151) and subjects with symptomatic apical periodontitis or acute apical abscess (n = 124). Subjects without AP (n = 169) and asymptomatic (n = 196) were used as controls, respectively. Saliva samples were collected as source of genomic DNA. Twelve SNPs in the TP63 gene were selected for genotyping using Taqman chemistry in real‐time PCR. Data analysis was performed using PLINK software. The Bonferroni method was applied to correct for multiple testing; α ≤ 0.004 indicates significant differences between groups. Results TP63 expression was evident in apical abscesses and radicular cysts, while weaker expression was observed in periapical granulomas. Positive expression was observed in mononuclear cells in the granulation tissues of all AP lesions. Regarding the presence of AP, a trend for allelic association was observed for rs16864812 and rs9810322 (P = 0.04) and rs9810322 genotypes were also nominally associated with AP under a dominant model (P = 0.04). When considering the presence of periapical pain, a trend for allelic and genotypic association was observed for rs10155037 (P = 0.03). Haplotypes were also associated with AP and periapical pain (P ≤ 0.05). Conclusions Apical periodontitis is a complex multifactorial condition and it is likely that multiple genes and environmental effects may influence its susceptibility, progression or both. TP63 variants may play a role in AP pathogenesis and susceptibility, individually or interactively with other genes. Additional studies in other populations and functional studies are needed to improve understanding of the role of TP63 in AP.

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“…It is known that ΔNp63α is the predominant isoform of p63 expressed in epithelial cells. Studies have shown that p63 proteins can function as transcription factors, controlling transcription of downstream genes, including p21, Bax, Puma, Dicer, MKP3, and genes involved in cell adhesion [5]. Consequently, p63 proteins play a key role in cell proliferation, survival, development and tumorigenesis [6].…”

Section: Introductionmentioning

confidence: 99%

p63α modulates c-Myc activity via direct interaction and regulation of MM1 protein stability

Han

et al. 2016

Oncotarget

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Both p53-related p63 and c-Myc are transcription factors playing key roles in cell proliferation, survival, development and tumorigenesis. In the present study, we identified that MM1, a c-Myc inhibitor, specifically binds to C-termini of p63β (including ΔNp63β and TAp63β). Further study demonstrates that p63β facilitates MM1 protein degradation via proteasomal pathway, resulting in elevation of c-Myc transactivation activity. Knockdown of ΔNp63β leads to decrease in c-Myc protein levels, concomitant with reduced expression of CDK4 and Cyclin D1, and impaired cell cycle progression, both of which are effectively reversed by simultaneous knockdown of MM1. Moreover, expression of p63 and CDK4 is concomitantly up-regulated in B-cell acute lymphoblastic leukemia. Together, this study reveals a novel crosstalk between p63 and c-Myc that may play an important role in cell cycle progression and tumorigenesis.

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Regulation of p63 Protein Stability via Ubiquitin-Proteasome Pathway

Cited by 26 publications

References 68 publications

Opposing Growth Regulatory Roles of Protein Kinase D Isoforms in Human Keratinocytes

Opposing Growth Regulatory Roles of Protein Kinase D Isoforms in Human Keratinocytes

Potential role of TP63 in apical periodontitis development

p63α modulates c-Myc activity via direct interaction and regulation of MM1 protein stability

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