Inhibition of the PP2A activity by the histone chaperone ANP32B is long-range allosterically regulated by respiratory cytochrome c

Rivero-Rodríguez F. ; Díaz-Quintana A. ; Velázquez-Cruz A. ; González-Arzola K. ; Gavilan M.P. ; Velázquez-Campoy A. (Universidad de Zaragoza) ; Ríos R.M. ; De la Rosa M.A. ; Díaz-Moreno I.

Resumen: Repair of injured DNA relies on nucleosome dismantling by histone chaperones and de-phosphorylation events carried out by Protein Phosphatase 2A (PP2A). Typical histone chaperones are the Acidic leucine-rich Nuclear Phosphoprotein 32 family (ANP32) members, e.g. ANP32A, which is also a well-known PP2A inhibitor (a.k.a. I1PP2A). Here we report the novel interaction between the endogenous family member B—so-called ANP32B—and endogenous cytochrome c in cells undergoing camptothecin-induced DNA damage. Soon after DNA lesions but prior to caspase cascade activation, the hemeprotein translocates to the nucleus to target the Low Complexity Acidic Region (LCAR) of ANP32B; in a similar way, our group recently reported that the hemeprotein targets the acidic domain of SET/Template Activating Factor-Iß (SET/TAF-Iß), which is another histone chaperone and PP2A inhibitor (a.k.a. I2PP2A). The nucleosome assembly activity of ANP32B is indeed unaffected by cytochrome c binding. Like ANP32A, ANP32B inhibits PP2A activity and is thus herein referred to as I3PP2A. Our data demonstrates that ANP32B-dependent inhibition of PP2A is regulated by respiratory cytochrome c, which induces long-distance allosteric changes in the structured N-terminal domain of ANP32B upon binding to the C-terminal LCAR. In agreement with the reported role of PP2A in the DNA damage response, we propose a model wherein cytochrome c is translocated from the mitochondria into the nucleus upon DNA damage to modulate PP2A activity via its interaction with ANP32B. © 2021 The Author(s)

Idioma: Inglés

DOI: 10.1016/j.redox.2021.101967

Año: 2021

Publicado en: Redox Biology 43 (2021), 101967 [17 pp]
ISSN: 2213-2317

Factor impacto JCR: 10.787 (2021)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 27 / 297 = 0.091 (2021) - Q1 - T1

Factor impacto CITESCORE: 16.4 - Biochemistry, Genetics and Molecular Biology (Q1)

Factor impacto SCIMAGO: 2.191 - Clinical Biochemistry (Q1) - Biochemistry (Q1)

Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2012-31670
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2015-71017-P-BMC
Financiación: info:eu-repo/grantAgreement/ES/MINECOPGC2018-096049-BI00

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)