Ubiquitin proteolysis of a CDK-related kinase regulates titan cell formation and virulence in the fungal pathogen Cryptococcus neoformans.
Ubiquitin proteolysis of a CDK-related kinase regulates titan cell formation and virulence in the fungal pathogen Cryptococcus neoformans.
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cdk相关激酶的泛素蛋白水解调节真菌病原体新隐球菌巨细胞的形成和毒力。
DOI：
10.1038/s41467-022-34151-6
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发表时间：
2022-10-27
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
Fungal pathogens often undergo morphological switches, including cell size changes, to adapt to the host environment and cause disease. The pathogenic yeast Cryptococcus neoformans forms so-called ‘titan cells’ during infection. Titan cells are large, polyploid, display alterations in cell wall and capsule, and are more resistant to phagocytosis and various types of stress. Titan cell formation is regulated by the cAMP/PKA signal pathway, which is stimulated by the protein Gpa1. Here, we show that Gpa1 is activated through phosphorylation by a CDK-related kinase (Crk1), which is targeted for degradation by an E3 ubiquitin ligase (Fbp1). Strains overexpressing CRK1 or an allele lacking a PEST domain exhibit increased production of titan cells similarly to the fbp1∆ mutant. Conversely, CRK1 deletion results in reduced titan cell production, indicating that Crk1 stimulates titan cell formation. Crk1 phosphorylates Gpa1, which then localizes to the plasma membrane and activates the cAMP/PKA signal pathway to induce cell enlargement. Furthermore, titan cell-overproducing strains trigger increased Th1 and Th17 cytokine production in CD4+ T cells and show attenuated virulence in a mouse model of systemic cryptococcosis. Overall, our study provides insights into the regulation of titan cell formation and fungal virulence. The pathogenic yeast Cryptococcus neoformans forms large, so-called ‘titan cells’ during infection. Here, Cao et al. show that a ubiquitin ligase inhibits this process by targeting for degradation a CDK-related kinase that stimulates titan cell formation.
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影响因子：
3.6
作者：
Xue C;Hsueh YP;Chen L;Heitman J
通讯作者：
Heitman J
DOI：
10.1042/bcj20160819
发表时间：
2018-11-09
期刊：
The Biochemical journal
影响因子：
--
作者：
Chakravorty D;Assmann SM
通讯作者：
Assmann SM
影响因子：
3.3
作者：
Bahn, YS;Kojima, K;Heitman, J
通讯作者：
Heitman, J
影响因子：
9.8
作者：
Di Talia S;Wang H;Skotheim JM;Rosebrock AP;Futcher B;Cross FR
通讯作者：
Cross FR
影响因子：
3.1
作者：
Cox, GM;Mukherjee, J;Perfect, JR
通讯作者：
Perfect, JR