STK35L1 regulates host cell cycle-related genes and is essential for Plasmodium infection during the liver stage of malaria.
Exp Cell Res
; 406(2): 112764, 2021 09 15.
Article
en En
| MEDLINE
| ID: mdl-34358525
ABSTRACT
Protein kinases of both the parasite and the host are crucial in parasite invasion and survival and might act as drug targets against drug-resistant malaria. STK35L1 was among the top five hits in kinome-wide screening, suggesting its role in malaria's liver stage. However, the role of host STK35L1 in malaria remains elusive. In this study, we found that STK35L1 was highly upregulated during the infection of Plasmodium berghei (P. berghei) in HepG2 cells and mice liver, and knockdown of STK35L1 remarkably suppressed the sporozoites' infection in HepG2 cells. We showed that STAT3 is upregulated and phosphorylated during P. berghei sporozoites' infection, and STAT3 activation is required for both the upregulation of STK35L1 and STAT3. Furthermore, we found that ten cell cycle genes were upregulated in the sporozoite-infected hepatocytes. Knockdown of STK35L1 inhibited the basal expression of these genes except CDKN3 and GTSE1 in HepG2 cells. Thus, we identified STK35L1 as a host kinase that plays an obligatory role in malaria's liver stage and propose that it may serve as a potential drug target against drug-resistant malaria.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Plasmodium berghei
/
Proteínas Serina-Treonina Quinasas
/
Proteínas de Ciclo Celular
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Esporozoítos
/
Factor de Transcripción STAT3
/
Hígado
/
Malaria
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Exp Cell Res
Año:
2021
Tipo del documento:
Article
País de afiliación:
India