The role of p63 in epidermal morphogenesis and neoplasia

2010 ◽  
Vol 38 (1) ◽  
pp. 223-228 ◽  
Author(s):  
Simon S. McDade ◽  
Dennis J. McCance
Keyword(s):  
Transcription Factors ◽  
Splice Variants ◽  
Family Members ◽  
Protein Isoforms ◽  
Structural Homology ◽  
P53 Family ◽  
Multiple Protein ◽  
Proliferation And Differentiation ◽  
Epidermal Morphogenesis

The p53 family of transcription factors is made up of p53, p63 and p73, which share significant structural homology. In particular, transcriptional complexity and the expression of multiple protein isoforms are an emergent trait of all family members. p63 is the evolutionarily eldest member of the p53 family and the various isoforms have critical roles in the development of stratifying epithelia. Recent results have uncovered additional splice variants, adding to the complexity of the transcriptional architecture of p63. These observations and the emerging extensive interplay between p63 and p53 in development, proliferation and differentiation underline the importance of considering all isoforms and family members in studies of the function of p53 family members.

scholarly journals The role of P63 in cancer, stem cells and cancer stem cells

2011 ◽  
Vol 16 (2) ◽  
Author(s):  
Marta Nekulova ◽  
Jitka Holcakova ◽  
Philip Coates ◽  
Borivoj Vojtesek
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Family Members ◽  
Adult Stem Cell ◽  
Epidermal Differentiation ◽  
Protein Isoforms ◽  
P53 Family ◽  
Stem Cell Regulation

AbstractThe transcription factor p63 has important functions in tumorigenesis, epidermal differentiation and stem cell self-renewal. The TP63 gene encodes multiple protein isoforms that have different or even antagonistic roles in these processes. The balance of p63 isoforms, together with the presence or absence of the other p53 family members, p73 and p53, has a striking biological impact. There is increasing evidence that interactions between p53-family members, whether cooperative or antagonistic, are involved in various cell processes. This review summarizes the current understanding of the role of p63 in tumorigenesis, metastasis, cell migration and senescence. In particular, recent data indicate important roles in adult stem cell and cancer stem cell regulation and in the response of cancer cells to therapy.

scholarly journals Drosophila p53 isoforms have overlapping and distinct functions in germline genome integrity and oocyte quality control

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Ananya Chakravarti ◽  
Heshani N Thirimanne ◽  
Savanna Brown ◽  
Brian R Calvi
Keyword(s):  
Quality Control ◽  
Family Members ◽  
P53 Gene ◽  
Genotoxic Stress ◽  
Oocyte Quality ◽  
Protein Isoforms ◽  
Dna Breaks ◽  
P53 Family ◽  
Dna Lesion ◽  
P53 Isoforms

p53 gene family members in humans and other organisms encode a large number of protein isoforms whose functions are largely undefined. Using Drosophila as a model, we find that a p53B isoform is expressed predominantly in the germline where it colocalizes with p53A into subnuclear bodies. It is only p53A, however, that mediates the apoptotic response to ionizing radiation in the germline and soma. In contrast, p53A and p53B are both required for the normal repair of meiotic DNA breaks, an activity that is more crucial when meiotic recombination is defective. We find that in oocytes with persistent DNA breaks p53A is also required to activate a meiotic pachytene checkpoint. Our findings indicate that Drosophila p53 isoforms have DNA lesion and cell type-specific functions, with parallels to the functions of mammalian p53 family members in the genotoxic stress response and oocyte quality control.

scholarly journals Present status and expectation of aristaless-related homeobox (ARX) in endocrine pancreas

2019 ◽  
Vol 63 (11-12) ◽  
pp. 579-587 ◽  
Author(s):  
Sai Xu ◽  
Ji-Ping Xu
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Endocrine Pancreas ◽  
Theoretical Foundation ◽  
Alpha Cell ◽  
Alpha Cells ◽  
Proliferation And Differentiation ◽  
Direct Target ◽  
Vertebrate Central Nervous System

The aristaless-related homeobox (ARX) gene has become one of most frequently mutated genes which is closely linked with development of the vertebrate central nervous system; however, the molecular and clinical bases of its function in the proliferation and differentiation of the endocrine pancreas have not, to date, been systematically characterized. ARX is considered as a regulator which determines endocrine cell fate and a bio-marker of the pancreatic α-cell. Disruption and mutation of ARX are found to lead to the deletion and reduction of α-cells both in mice models and in humans. Furthermore, expression of ARX is regulated by multiple transcription factors involved in development of the pancreas, such as Ngn3, Isl1, Nkx2.2 and Nkx6.1. Taken together, given the vital importance of glucagon in diabetes treatment, it is possible that ARX may down-regulate exorbitant glucagon levels by reducing the number of α-cells as a direct target; thus, the role of ARX in the maintenance of α-cell identity and quantity should be investigated and summarized. This article mainly focuses on the role of ARX in the endocrine pancreas, introduces the ARX-related animal model and transcription factors, and highlights the latest advances in our understanding in order to provide a clearer theoretical foundation for future scientific research.

scholarly journals IFI16Expression Is Related to Selected Transcription Factors during B-Cell Differentiation

2015 ◽  
Vol 2015 ◽  
pp. 1-20 ◽  
Author(s):  
Pier Paolo Piccaluga ◽  
Claudio Agostinelli ◽  
Fabio Fuligni ◽  
Simona Righi ◽  
Claudio Tripodo ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
B Cell ◽  
Peripheral Blood Lymphocytes ◽  
B Cell Differentiation ◽  
Cellular Survival ◽  
Human B Cells ◽  
Proliferation And Differentiation ◽  
B Cell Subsets

The interferon-inducible DNA sensor IFI16 is involved in the modulation of cellular survival, proliferation, and differentiation. In the hematopoietic system, IFI16 is consistently expressed in the CD34+ stem cells and in peripheral blood lymphocytes; however, little is known regarding its regulation during maturation of B- and T-cells. We explored the role of IFI16 in normal B-cell subsets by analysing its expression and relationship with the major transcription factors involved in germinal center (GC) development and plasma-cell (PC) maturation.IFI16mRNA was differentially expressed in B-cell subsets with significant decrease inIFI16mRNA in GC and PCs with respect to naïve and memory subsets.IFI16mRNA expression is inversely correlated with a few master regulators of B-cell differentiation such asBCL6, XBP1, POU2AF1, andBLIMP1. In contrast,IFI16expression positively correlated withSTAT3, REL, SPIB, RELA, RELB, IRF4, STAT5B, andSTAT5A. ARACNE algorithm indicated a direct regulation ofIFI16byBCL6,STAT5B, andRELB, whereas the relationship betweenIFI16and the other factors is modulated by intermediate factors. In addition, analysis of the CD40 signaling pathway showed thatIFI16gene expression directly correlated with NF-κB activation, indicating that IFI16 could be considered an upstream modulator of NF-κB in human B-cells.

scholarly journals Reciprocal cross-regulation of VND and SND multigene TF families for wood formation in Populus trichocarpa

2017 ◽  
Vol 114 (45) ◽  
pp. E9722-E9729 ◽  
Author(s):  
Ying-Chung Jimmy Lin ◽  
Hao Chen ◽  
Quanzi Li ◽  
Wei Li ◽  
Jack P. Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Splice Variant ◽  
Reciprocal Cross ◽  
Splice Variants ◽  
Family Members ◽  
Wood Formation ◽  
Negative Regulator ◽  
General Mechanism ◽  
Nac Domain

Secondary cell wall (SCW) biosynthesis is the biological process that generates wood, an important renewable feedstock for materials and energy. NAC domain transcription factors, particularly Vascular-Related NAC-Domain (VND) and Secondary Wall-Associated NAC Domain (SND) proteins, are known to regulate SCW differentiation. The regulation of VND and SND is important to maintain homeostasis for plants to avoid abnormal growth and development. We previously identified a splice variant, PtrSND1-A2IR, derived from PtrSND1-A2 as a dominant-negative regulator, which suppresses the transactivation of all PtrSND1 family members. PtrSND1-A2IR also suppresses the self-activation of the PtrSND1 family members except for its cognate transcription factor, PtrSND1-A2, suggesting the existence of an unknown factor needed to regulate PtrSND1-A2. Here, a splice variant, PtrVND6-C1IR, derived from PtrVND6-C1 was discovered that suppresses the protein functions of all PtrVND6 family members. PtrVND6-C1IR also suppresses the expression of all PtrSND1 members, including PtrSND1-A2, demonstrating that PtrVND6-C1IR is the previously unidentified regulator of PtrSND1-A2. We also found that PtrVND6-C1IR cannot suppress the expression of its cognate transcription factor, PtrVND6-C1. PtrVND6-C1 is suppressed by PtrSND1-A2IR. Both PtrVND6-C1IR and PtrSND1-A2IR cannot suppress their cognate transcription factors but can suppress all members of the other family. The results indicate that the splice variants from the PtrVND6 and PtrSND1 family may exert reciprocal cross-regulation for complete transcriptional regulation of these two families in wood formation. This reciprocal cross-regulation between families suggests a general mechanism among NAC domain proteins and likely other transcription factors, where intron-retained splice variants provide an additional level of regulation.

scholarly journals Revised Exon Structure of l-DOPA Decarboxylase (DDC) Reveals Novel Splice Variants Associated with Colorectal Cancer Progression

2020 ◽  
Vol 21 (22) ◽  
pp. 8568
Author(s):  
Pinelopi I. Artemaki ◽  
Maria Papatsirou ◽  
Michaela A. Boti ◽  
Panagiotis G. Adamopoulos ◽  
Spyridon Christodoulou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Prognostic Value ◽  
Splice Variants ◽  
Protein Isoforms ◽  
Dopa Decarboxylase ◽  
Colorectal Cancer Progression ◽  
Next Generation Sequencing Ngs ◽  
Exon Structure

Colorectal cancer (CRC) is a highly heterogenous malignancy with an increased mortality rate. Aberrant splicing is a typical characteristic of CRC, and several studies support the prognostic value of particular transcripts in this malignancy. l-DOPA decarboxylase (DDC) and its derivative neurotransmitters play a multifaceted role in physiological and pathological states. Our recent data support the existence of 6 DDC novel exons. In this study, we investigated the existence of additional DDC novel exons and transcripts, and their potential value as biomarkers in CRC. Next-generation sequencing (NGS) in 55 human cell lines coupled with Sanger sequencing uncovered 3 additional DDC novel exons and 20 splice variants, 7 of which likely encode new protein isoforms. Eight of these transcripts were detected in CRC. An in-house qPCR assay was developed and performed in TNM II and III CRC samples for the quantification of transcripts bearing novel exons. Extensive biostatistical analysis uncovered the prognostic value of specific DDC novel exons for patients’ disease-free and overall survival. The revised DDC exon structure, the putative protein isoforms with distinct functions, and the prognostic value of novel exons highlight the pivotal role of DDC in CRC progression, indicating its potential utility as a molecular biomarker in CRC.

Role of p53 family members p73 and p63 in human hematological malignancies

2012 ◽  
Vol 53 (11) ◽  
pp. 2116-2129 ◽  
Author(s):  
Evguenia M. Alexandrova ◽  
Ute M. Moll
Keyword(s):  
Hematological Malignancies ◽  
Family Members ◽  
P53 Family

scholarly journals The Role of AP-1 Transcription Factors in Plasma Cell Biology and Multiple Myeloma Pathophysiology

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2326
Author(s):  
Fengjuan Fan ◽  
Klaus Podar
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Transcription Factors ◽  
Cell Differentiation ◽  
Plasma Cell ◽  
Cell Biology ◽  
Hematologic Malignancy ◽  
Family Members ◽  
Plasma Cell Differentiation

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the clonal expansion of malignant plasma cells within the bone marrow. Activator Protein-1 (AP-1) transcription factors (TFs), comprised of the JUN, FOS, ATF and MAF multigene families, are implicated in a plethora of physiologic processes and tumorigenesis including plasma cell differentiation and MM pathogenesis. Depending on the genetic background, the tumor stage, and cues of the tumor microenvironment, specific dimeric AP-1 complexes are formed. For example, AP-1 complexes containing Fra-1, Fra-2 and B-ATF play central roles in the transcriptional control of B cell development and plasma cell differentiation, while dysregulation of AP-1 family members c-Maf, c-Jun, and JunB is associated with MM cell proliferation, survival, drug resistance, bone marrow angiogenesis, and bone disease. The present review article summarizes our up-to-date knowledge on the role of AP-1 family members in plasma cell differentiation and MM pathophysiology. Moreover, it discusses novel, rationally derived approaches to therapeutically target AP-1 TFs, including protein-protein and protein-DNA binding inhibitors, epigenetic modifiers and natural products.

scholarly journals The signal transducer and activator of transcription factors lodge in immunopathogenesis of rheumatoid arthritis

Reumatismo ◽  
2016 ◽  
Vol 67 (4) ◽  
pp. 127 ◽  
Author(s):  
F. Zare ◽  
M. Dehghan-Manshadi ◽  
A. Mirshafiey
Keyword(s):  
Transcription Factors ◽  
Family Members ◽  
Bone Destruction ◽  
Autoimmune Disorder ◽  
Organ Damage ◽  
Signal Transducer ◽  
Necrosis Factor Alpha ◽  
Autoantibody Production ◽  
Factor Alpha

Rheumatoid arthritisis (RA) is a chronic autoimmune disorder that affects ~1-2% of the world’s population and damages synovial joints. RA is characterized by inflammation, autoantibody production, cartilage and bone destruction and synovial hyperplasia. Inflammation induces systemic and articular synthesis of pro-inflammatory cytokines, such as tumor necrosis factor alpha and interleukin-6 that play essential roles in joint and other organ damage in this disease. Considering the role of signal transducer and activator of transcription factors (STATs) in signaling of these cytokines, these proteins may be involved in the pathogenesis of RA. The expression and activity of STATs can contribute to the onset, progression and severity of RA. All STAT family members (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6) have been associated with autoimmune diseases, as highlighted in several studies. In this review we aim to describe the immunobiology of STATs and its family members and the role of these proteins in the immunopathogenesis of RA.

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