The role of p53/p73 family members in the cytotoxic response

p53/p73 家族成员在细胞毒性反应中的作用

• 批准号: MC_UU_00025/2
• 负责人: Gerry Melino
• 金额: $ 444.44万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00025%2F2
• 关键词: role; p53; p73; family; members

Toxic insult arising from environmental, occupational or therapeutic exposure, is a primary cause of disease and the treatment of these disorders has significant medical, social and economic implications for the UK population. The p53 family of proteins (p53, p63 and p73) is considered as a master regulator in vertebrates, and pathways that it controls range from developmental and homeostatic functions to the remarkable role in cancer. In particular, a predominant aspect of p53 family function in tumourigenesis is the ability to control the cellular stress response. This represents a pivotal aspect in the response to toxic insult.The overall aim of the Laboratory is to understand the fundamental mechanisms of cellular and tissue response to injury caused by drugs, chemicals and endogenous molecules, e.g. free radicals. Therefore, using both genetically modified mouse model and high throughput analysis, we aim to investigate:1) How environmental exposure drives tumour progression;2) How these transcription factors regulate the response to toxic insult;Moreover, we are dedicated to the development of chemicals compounds that can regulate expression and function of the p53 family members. This could have potential therapeutic applications.

由环境、职业或治疗暴露引起的毒性损伤是疾病的主要原因，这些疾病的治疗对英国人口具有重大的医疗、社会和经济影响。p53蛋白家族（p53，p63和p73）被认为是脊椎动物中的主要调节因子，其控制的途径范围从发育和稳态功能到癌症中的显着作用。特别地，p53家族在肿瘤发生中的功能的主要方面是控制细胞应激反应的能力。本实验室的整体目标是了解细胞和组织对药物、化学品和内源性分子（如自由基）造成的损伤的反应的基本机制。因此，使用转基因小鼠模型和高通量分析，我们的目标是研究：1）环境暴露如何驱动肿瘤进展;2）这些转录因子如何调节对毒性损伤的反应;此外，我们致力于开发可以调节p53家族成员表达和功能的化学化合物。这可能具有潜在的治疗应用。

项目成果

p53 mutants cooperate with HIF-1 in transcriptional regulation of extracellular matrix components to promote tumor progression.

• DOI: 10.1073/pnas.1808314115
• 发表时间: 2018-11-13
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Amelio I;Mancini M;Petrova V;Cairns RA;Vikhreva P;Nicolai S;Marini A;Antonov AA;Le Quesne J;Baena Acevedo JD;Dudek K;Sozzi G;Pastorino U;Knight RA;Mak TW;Melino G
• 通讯作者: Melino G

Myoblasts rely on TAp63 to control basal mitochondria respiration.

• DOI: 10.18632/aging.101668
• 发表时间: 2018-11-28
• 期刊: Aging
• 作者: Ciuffoli V;Lena AM;Gambacurta A;Melino G;Candi E
• 通讯作者: Candi E

Lipid metabolism offers anticancer treatment by regulating ferroptosis.

脂质代谢通过调节铁死亡提供抗癌治疗。

• DOI: 10.1038/s41418-019-0418-2
• 发表时间: 2019
• 期刊: Cell death and differentiation
• 影响因子: 12.4
• 作者: Carbone M

Erratum: Actin-binding protein alpha-actinin 4 (ACTN4) is a transcriptional co-activator of RelA/p65 sub-unit of NF-kB.

• DOI: 10.18632/oncotarget.26206
• 发表时间: 2018-09-28
• 期刊: Oncotarget
• 作者: Aksenova V;Turoverova L;Khotin M;Magnusson KE;Tulchinsky E;Melino G;Pinaev GP;Barlev N;Tentler D
• 通讯作者: Tentler D