CK2 is a Ser/Thr protein kinase essential for cell viability whose activity is anomalously high in several cancers. CK2 is a validated target for cancer therapy with one small molecule inhibitor in phase I clinical trials. This enzyme is not regulated by mechanisms common to other protein kinases, and how its activity is controlled is still unclear. We present a new crystal structure of the CK2 holoenzyme that supports an autoinhibitory mechanism of regulation whereby the β-subunit plays an essential role in the formation of inactive polymeric assemblies. The derived structural model of (down)regulation by aggregation contributes to the interpretation of biochemical and functional data and paves the way for new strategies in the modulation of CK2 activity and for the design of non-ATP-competitive inhibitors targeting the interaction between the α catalytic and the β regulatory subunits.

Structural Determinants of Protein Kinase CK2 Regulation by Autoinhibitory Polymerization / Lolli, Graziano; Pinna, Lorenzo A.; Battistutta, Roberto. - In: ACS CHEMICAL BIOLOGY. - ISSN 1554-8929. - STAMPA. - 7:(2012), pp. 1158-1163. [10.1021/cb300054n]

Structural Determinants of Protein Kinase CK2 Regulation by Autoinhibitory Polymerization

Graziano Lolli;
2012-01-01

Abstract

CK2 is a Ser/Thr protein kinase essential for cell viability whose activity is anomalously high in several cancers. CK2 is a validated target for cancer therapy with one small molecule inhibitor in phase I clinical trials. This enzyme is not regulated by mechanisms common to other protein kinases, and how its activity is controlled is still unclear. We present a new crystal structure of the CK2 holoenzyme that supports an autoinhibitory mechanism of regulation whereby the β-subunit plays an essential role in the formation of inactive polymeric assemblies. The derived structural model of (down)regulation by aggregation contributes to the interpretation of biochemical and functional data and paves the way for new strategies in the modulation of CK2 activity and for the design of non-ATP-competitive inhibitors targeting the interaction between the α catalytic and the β regulatory subunits.
2012
Lolli, Graziano; Pinna, Lorenzo A.; Battistutta, Roberto
Structural Determinants of Protein Kinase CK2 Regulation by Autoinhibitory Polymerization / Lolli, Graziano; Pinna, Lorenzo A.; Battistutta, Roberto. - In: ACS CHEMICAL BIOLOGY. - ISSN 1554-8929. - STAMPA. - 7:(2012), pp. 1158-1163. [10.1021/cb300054n]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/284392
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 21
  • Scopus 58
  • ???jsp.display-item.citation.isi??? 56
social impact