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BRAF and IKKα involvement in DNA Damage Response

ABSTRACT: BRAF and IKKα are damage-responsive kinases required for 53BP1 and RIF1 co-recruitment to sites of DNA breaks and for timely resolution of DNA lesions. This provides a novel therapeutic opportunity based on combining BRAF or IKKα inhibitors with therapeutic agents that induce DNA damage

INSTRUMENT(S): Orbitrap Fusion Lumos, LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: Eva Borràs

LAB HEAD: Eduard Sabido

PROVIDER: PXD008932 | Pride | 2019-11-14

REPOSITORIES: Pride

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Publications

IKKα Kinase Regulates the DNA Damage Response and Drives Chemo-resistance in Cancer.

Colomer Carlota C Margalef Pol P Villanueva Alberto A Vert Anna A Pecharroman Irene I Solé Laura L González-Farré Mónica M Alonso Josune J Montagut Clara C Martinez-Iniesta Maria M Bertran Joan J Borràs Eva E Iglesias Mar M Sabidó Eduard E Bigas Anna A Boulton Simon J SJ Espinosa Lluís L

Molecular cell 20190710 4

Phosphorylated IKKα(p45) is a nuclear active form of the IKKα kinase that is induced by the MAP kinases BRAF and TAK1 and promotes tumor growth independent of canonical NF-κB signaling. Insights into the sources of IKKα(p45) activation and its downstream substrates in the nucleus remain to be defined. Here, we discover that IKKα(p45) is rapidly activated by DNA damage independent of ATM-ATR, but dependent on BRAF-TAK1-p38-MAPK, and is required for robust ATM activation and efficient DNA repair. ...[more]

PMID: 31302002

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