Elucidating the interaction of C-terminal domain of Vaccinia-Related Kinase 2A (VRK2A) with B-cell lymphoma-extra Large (Bcl-xL) to decipher its anti-apoptotic role in cancer.
Biochem J
; 480(22): 1871-1885, 2023 11 29.
Article
em En
| MEDLINE
| ID: mdl-37943248
ABSTRACT
Vaccinia-Related Kinase 2 (VRK2) is an anti-apoptotic Ser/Thr kinase that enhances drug sensitivity in cancer cells. This protein exists in two isoforms VRK2A, the longer variant, and VRK2B, which lacks the C-terminal region and transmembrane domain. While the therapeutic importance of VRK2 family proteins is known, the specific roles of VRK2A and its interplay with apoptotic regulator Bcl-xL (B-cell lymphoma-extra Large) remain elusive. Bcl-xL regulates cell death by interacting with BAX (B-cell lymphoma-2 Associated X-protein), controlling its cellular localization and influencing BAX-associated processes and signaling pathways. As VRK2A interacts with the Bcl-xL-BAX complex, comprehending its regulatory engagement with Bcl-xL presents potential avenues for intervening in diseases. Using a multi-disciplinary approach, this study provides information on the cellular localization of VRK2A and establishes its interaction with Bcl-xL in the cellular milieu, pinpointing the interacting site and elucidating its anti-apoptotic property within the complex. Furthermore, this study also put forth a model that highlights the importance of VRK2A in stabilizing the ternary complex, formed with Bcl-xL and BAX, thereby impeding BAX dissociation and hence apoptosis. Therefore, further investigations associated with this important revelation will provide cues for designing cancer therapeutics in the future.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfoma de Células B
/
Proteína bcl-X
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article