TAp63 Is a Master Transcriptional Regulator of Lipid and Glucose Metabolism

Su, Xiaohua; Gi, Young Jin; Chakravarti, Deepavali; Chan, Io Long; Zhang, Aijun; Xia, Xuefeng; Tsai, Kenneth Y.; Flores, Elsa R.

doi:10.1016/j.cmet.2012.09.006

Cited by 99 publications

(139 citation statements)

References 44 publications

Supporting

Mentioning

135

Contrasting

Unclassified

Order By: Relevance

“…In the first transgenic model, Suh et al, reported no embryonic development defect (Suh et al, 2006). Yet, the second KO mouse strain had a strong proportion of embryonic lethality (Su et al, 2012). These data show that some modifier genes may amplify or neutralize the lack of TAp63, depending on the genetic background of murine strains.…”

Section: P63 and Heart Developmentmentioning

confidence: 93%

See 1 more Smart Citation

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

Section: P63 and Heart Developmentmentioning

confidence: 93%

“…TAp63 responds to metformin, the drug used to treat Type 2 diabetes. In particular, TAp63g variant increases following metformin administration (Su et al, 2012). Moreover, TAp63 null mice are prone to metastatic tumors.…”

Section: P63 and Metabolismmentioning

confidence: 99%

P63 in health and cancer

Gonfloni

Caputo²,

Iannizzotto³

2015

Int. J. Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Performing chromatin immunoprecipitation using antibodies for the various isoforms of the p53 family coupled with next-generation sequencing (ChIPSeq) in discrete stem cell compartments within the skin and during development or after various stresses will be key to understanding transcriptional regulation by this family of genes. Recently, roles for p63 and p73 in metabolism have been identified (Flores and Lozano 2012;Rufini et al 2012;Su et al 2012) and understanding how the p53 family influences the cellular metabolism of skin cells will be an area of new research.…”

Section: Discussionmentioning

confidence: 99%

p53/p63/p73 in the Epidermis in Health and Disease

Botchkarev

Flores

2014

Cold Spring Harbor Perspectives in Medicine

View full text Add to dashboard Cite

Although p53 has long been known as the "guardian of the genome" with a role in tumor suppression in many tissues, the discovery of two p53 ancestral genes, p63 and p73, more than a decade ago has triggered a considerable amount of research into the role of these genes in skin development and diseases. In this review, we primarily focus on mechanisms of action of p53 and p63, which are the best-studied p53 family members in the skin. The existence of multiple isoforms and their roles as transcriptional activators and repressors are key to their function in multiple biological processes including the control of skin morphogenesis, regeneration, tumorigenesis, and response to chemotherapy. Last, we provide directions for further research on this family of genes in skin biology and pathology.

show abstract

“…30,31 In contrast, analysis of TAp63-specific knockout mice has revealed that this isoform has diverse functions, including the protection of female germ cells from apoptosis, 32 prevention of metastasis of epithelial tumors, 33 and suppression of aging and obesity. 30,34 However, as both TAp63 and DNp63 can be alternatively spliced at the carboxyterminus to produce a-, b-, c-, d-, and e-isoforms, 35,36 further investigation is needed to elucidate specific functions of each specific isoform. Notably, however, DNp63a is the dominant isoform expressed in the basal layer of epithelial tissues 35 and has been the focus in epithelial SC biology.…”

Section: Maintenance Of Epidermal Stem Cellsmentioning

confidence: 99%

Epidermal Stem Cells in Homeostasis and Wound Repair of the Skin

Senoo

2013

Advances in Wound Care

View full text Add to dashboard Cite

Significance: The skin interfollicular epidermis (IFE) is an organism's first line of defense against a harmful environment and physical damage. During homeostasis and wound repair, the IFE is rejuvenated constantly by IFE stem cells (SCs) that are capable of both proliferation and differentiation. However, the identity and behavior of IFE SCs remain controversial. Recent Advances: Two opposing theories exist regarding homeostasis of the IFE. On the basis of morphological and proliferative characteristics, one posits that the IFE is composed of a discrete epidermal proliferative unit comprised of *10 transit-amplifying (TA) cells and a centrally located SC in the basal layer. The other suggests that homeostasis of the IFE is maintained by a single progenitor population in the basal layer. A recent study has challenged these two apparently distinct models and demonstrated that the basal layer of the IFE contains both SCs and TA cells, which make distinct contributions to tissue homeostasis and repair. Moreover, phosphorylation levels of the transcription factor p63, the master regulator of the proliferative potential of epidermal SCs, can be used to distinguish self-renewing SCs from TA cells with more limited proliferative potential. Critical Issues: As technologies advance, IFE SCs can be identified at a singlecell level. Refinements of their identification and characterization are critical, not only for SC biology but also for the development of novel clinical applications. Future Directions: Understanding the signaling pathways that control selfrenewal and differentiation of IFE SCs will aid in developing novel cell-based therapeutics targeting degenerative epidermal diseases and wound repair. SCOPE AND SIGNIFICANCEIn this review, I discuss some of the major findings that have advanced our understanding of the behavior of epidermal stem cells (SCs) and their immediate progeny, transitamplifying (TA) cells. Particular emphasis is paid to those in the interfollicular epidermis (IFE), in light of their importance in homeostasis and tissue regeneration after injury. I also discuss the recent key findings on the regulation of p63, a transcription factor essential for the maintenance of the proliferative potential of epithelial SCs in both homeostatic and disease conditions of the epidermis, such as chronic wound healing. TRANSLATIONAL RELEVANCEThe role of epidermal SCs in contributing to homeostatic maintenance of the skin and wound repair has been well acknowledged for many years. Over the past decade, characterization of SCs and their differentiating progeny has been successfully refined, owing to the development of nucleotidelabeling and lineage-tracing methodologies. Elucidating the molecular mechanisms controlling the behavior of these cell types will provide novel strategies for the treatment of traumatic and degenerative skin diseases. As p63 is highly expressed in SCs of other epithelial tissues as well as many types of tumors of epithelial origin, these studies will also contribute to our understanding of...

show abstract

TAp63 Is a Master Transcriptional Regulator of Lipid and Glucose Metabolism

Cited by 99 publications

References 44 publications

P63 in health and cancer

P63 in health and cancer

p53/p63/p73 in the Epidermis in Health and Disease

Epidermal Stem Cells in Homeostasis and Wound Repair of the Skin

Contact Info

Product

Resources

About