Proteomics

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Downregulation of LATS kinases alters p53 to promote cell migration


ABSTRACT: p53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in non-transformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-κB subunit. Moreover, it partly shifts p53’s conformation and transcriptional output towards a state resembling cancer-associated p53 mutants, and endow p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are frequently downregulated in breast cancer; we propose that such downregulation might benefit cancer by converting p53 from a tumor suppressor into a tumor facilitator.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo sapiens  

TISSUE(S): Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Yair Pozniak  

LAB HEAD: Tamar Geiger

PROVIDER: PXD003120 | Pride | 2018-10-25

REPOSITORIES: pride

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Publications

Down-regulation of LATS kinases alters p53 to promote cell migration.

Furth Noa N   Bossel Ben-Moshe Noa N   Pozniak Yair Y   Porat Ziv Z   Geiger Tamar T   Domany Eytan E   Aylon Yael Y   Oren Moshe M  

Genes & development 20151101 22


p53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in nontransformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-κB subunit. Moreover, it partly shifts p53's conformation and transcriptional output toward a state resembling cancer-associated p53 mutants and endows p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are  ...[more]

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