Cif type III effector protein: A smart hijacker of the host cell cycle

Abstract

During coevolution with their hosts, bacteria have developed functions that allow them to interfere with the mechanisms controlling the proliferation of eukaryotic cells. Cycle inhibiting factor (Cif) is one of these cyclomodulins, the family of bacterial effectors that interfere with the host cell cycle. Acquired early during evolution by bacteria isolated from vertebrates and invertebrates, Cif is an effector protein of type III secretion machineries. Cif blocks the host cell cycle in G1 and G2 by inducing the accumulation of the cyclin-dependent kinase inhibitors p21^waf1/cip1 and p27^kip1. The x-ray crystal structure of Cif reveals it to be a divergent member of a superfamily of enzymes including cysteine proteases and acetyltransferases. This review summarizes and discusses what we know about Cif, from the bacterial gene to the host target.

Keywords:

• bacterial effector
• CDK
• cell cycle
• Cif
• cyclomodulin
• cysteine protease
• LEE
• p21^waf1
• p27^kip1
• T3SS

Acknowledgements

We thank Dr O Baron for helpful assistance in drawing Figure 2.

Financial & competing interests disclosure

Ascel Samba-Louaka was the recipient of a fellowship from the French ministry of research. Work done in the authors‘ laboratory was supported by a grant from the Agence Nationale pour la Recherche (ANR-05-MIIM-009) and by grants from the Ligue Nationale Contre le Cancer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Ascel Samba-Louaka was the recipient of a fellowship from the French ministry of research. Work done in the authors‘ laboratory was supported by a grant from the Agence Nationale pour la Recherche (ANR-05-MIIM-009) and by grants from the Ligue Nationale Contre le Cancer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.