Targeting p73 in cancer

Maas, Anna-Maria; Bretz, Anne Catherine; Mack, Elisabeth; Stiewe, Thorsten

doi:10.1016/j.canlet.2011.07.030

Cited by 37 publications

(37 citation statements)

References 91 publications

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“…39 Although the tumor suppressor function of p63 is still debated 40 and its role in tumorigenesis seems to be more that of an oncogene (overexpression of DNp63a in squamous cell carcinomas 41 ), the tumor suppressor function of p73 is well established. 17,42 This suggests that p73 is, despite its high sequence identity with p63, functionally closer related to p53. This functional resemblance is potentially also reflected in similar mechanisms of regulation ( Figure 6).…”

Section: Discussionmentioning

confidence: 97%

Analysis of the oligomeric state and transactivation potential of TAp73α

et al. 2013

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The proteins p73 and p63 are members of the p53 protein family and are involved in important developmental processes. Their high sequence identity with the tumor suppressor p53 has suggested that they act as tumor suppressors as well. While p63 has a crucial role in the maintenance of epithelial stem cells and in the quality control of oocytes without a clear role as a tumor suppressor, p73 0 s tumor suppressor activity is well documented. In a recent study we have shown that the transcriptional activity of TAp63a, the isoform responsible for the quality control in oocytes, is regulated by its oligomeric state. The protein forms an inactive, dimeric and compact conformation in resting oocytes, while the detection of DNA damage leads to the formation of an active, tetrameric and open conformation. p73 shows a high sequence identity to p63, including those domains that are crucial in stabilizing its inactive state, thus suggesting that p73's activity might be regulated by its oligomeric state as well. Here, we have investigated the oligomeric state of TAp73a by size exclusion chromatography and detailed domain interaction mapping, and show that in contrast to p63, TAp73a is a constitutive open tetramer. However, its transactivation potential depends on the cellular background and the promoter context. These results imply that the regulation of p73 0 s transcriptional activity might be more closely related to p53 than to p63.

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Section: Discussionmentioning

confidence: 97%

Analysis of the oligomeric state and transactivation potential of TAp73α

et al. 2013

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“…In addition, at least in the triple-negative tumor, IL30 substantially upregulates SHH, which accelerates MDA-MB-231 cell proliferation (42) and is fundamental in the maintenance of a putative cancer stem cell compartment along with MYC, which is also upregulated by IL30 (43,44). Moreover, IL30 downmodulates a set of critical tumor suppressors such as PTEN (18), RARB (19), RASSF1 (20), SLIT2 (21), and particularly TP73 (22), which lead to alterations in the cell-cycle regulation and a defective apoptotic response. Within the breast cancer genes whose expression is substantially increased by IL30 treatment, leptin, an adipocyte-derived adipokine, has been recently recognized to be fundamental in linking obesity and cancer (45).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-30 Promotes Breast Cancer Growth and Progression

et al. 2016

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The inflammatory tissue microenvironment that promotes the development of breast cancer is not fully understood. Here we report a role for elevated IL30 in supporting the breast cancer cell viability and invasive migration. IL30 was absent in normal mammary ducts, ductules, and acini of histologically normal breast and scanty in the few stromal infiltrating leukocytes. In contrast, IL30 was expressed frequently in breast cancer specimens where it was associated with triple-negative and HER2 þ molecular subtypes. In stromal leukocytes found in primary tumors or tumor-draining lymph nodes, which included mainly CD14 þ monocytes, CD68 þ macrophages, and

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“…In contrast to p53, mutations of the p63 gene cause numerous ectodermal dysplasia syndromes also associated with craniofacial and limb abnormalities (for review, see Rinne et al 2007;Vanbokhoven et al 2011). Unlike p53 and p63, mutations in the p73 gene are extremely rare; however, p73 is inactivated in cancers epigenetically, that is, via hypermethylation of its promoter (Maas et al 2013).…”

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confidence: 99%

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

Botchkarev

Flores

2014

Cold Spring Harbor Perspectives in Medicine

101

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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.

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Targeting p73 in cancer

Cited by 37 publications

References 91 publications

Analysis of the oligomeric state and transactivation potential of TAp73α

Analysis of the oligomeric state and transactivation potential of TAp73α

Interleukin-30 Promotes Breast Cancer Growth and Progression

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

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