Please use this identifier to cite or link to this item: https://doi.org/10.1242/bio.028225
Title: Characterisation of cellular effects of Burkholderia pseudomallei cycle inhibiting factor (Cif)
Authors: Ng M.Y. 
Gan Y.-H. 
Hagen T. 
Keywords: Burkholderia pseudomallei
Cullin RING E3 ubiquitin ligase
Cycle inhibiting factor
NF-?B
Issue Date: 2018
Publisher: Company of Biologists Ltd
Citation: Ng M.Y., Gan Y.-H., Hagen T. (2018). Characterisation of cellular effects of Burkholderia pseudomallei cycle inhibiting factor (Cif). Biology Open 7 (7) : bio28225. ScholarBank@NUS Repository. https://doi.org/10.1242/bio.028225
Abstract: Cycle inhibiting factors (Cifs) are type III secretion system effectors produced by some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Through their deamidase activity, Cifs inhibit the activity of Cullin RING E3 ubiquitin ligases (CRL). CRL inhibition induces the accumulation of cell cycle inhibitors p21 and p27, thereby leading to host cell cycle arrest. However, whether Cif exerts additional effects on host cells that are important in bacterial pathogenesis is currently poorly understood. In this study, we found that Cif exerts a bimodal effect on NF-?B signalling. Cif increases basal NF-?B activity. This effect is dependent on Cif-mediated activation of ERK MAPK. On the other hand, Cif inhibits NF-?B activation by TNF? and Burkholderia thailandensis infection. This inhibitory effect on NF-?B activity is partially mediated by Cif-dependent inhibition of CRLs. We also found that Cif only has a modest effect in stimulating the intracellular replication of the B. pseudomallei surrogate, B. thailandensis. The observed Cif-dependent stimulation of B. thailandensis intracellular replication was not, or was only partially, due to CRL inhibition. Furthermore, the increased B. thailandensis replication induced by Cif was independent of ERK MAPK activation. Our findings suggest that Cif likely exerts additional cellular effects through novel targets.
Source Title: Biology Open
URI: http://scholarbank.nus.edu.sg/handle/10635/152208
ISSN: 20466390
DOI: 10.1242/bio.028225
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