STK35L1 regulates host cell cycle-related genes and is essential for Plasmodium infection during the liver stage of malaria

Journal Article · Wed Sep 15 04:00:00 EDT 2021 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2021.112764· OSTI ID:23195519

Sharma, Phulwanti Kumari ^[1]; Kalia, Inderjeet ^[2]; Kaushik, Vibha ^[1]; Brünnert, Daniela ^[3]; Quadiri, Afshana; Kashif, Mohammad ^[2]; Chahar, Kirti Raj ^[1]; Agrawal, Akhil ^[4]; Goyal, Pankaj ^[1]

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1. Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Kishangarh, Rajasthan, 305 817 (India)
2. National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067 (India)
3. Experimental Tumor Immunology, Department of Obstetrics and Gynecology, University of Würzburg Medical School, Würzburg (Germany)
4. Department of Microbiology, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Kishangarh, Rajasthan, 305 817 (India)

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.

• OSTI ID: 23195519
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 406; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL CYCLE
DRUGS
GENES
LIVER
LIVER CELLS
MALARIA
MICE
PHOSPHOTRANSFERASES
PLASMODIUM
SCREENING