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PROSITE documentation PDOC51984

Cryptic Polo-Box 1 and 2 (CPB1 and CPB2) domains profiles





Description

The Polo-like kinase (Plk) family of proteins functions as master regulators of cell-cycle progression, cell division, centrosome maturation, and centriole duplication. All four members (Plk14) of this serine/threonine protein kinase family share sequence similarity and domain structure with the founding member, Drosophila Polo kinase (the homolog of human Plk1). Plks are highly expressed in proliferating cells and are overexpressed in a variety of cancers where they have the potential to promote chromosomal instability and tumorigenesis. Like Polo, Plk members regulate cell-cycle events that collectively include spindle formation, the metaphase-to-anaphase transition, mitotic exit, cytokinesis, and DNA damage checkpoints [1,2,3,4].

All Plks contain an amino-terminal serine/threonine kinase domain (see <PDOC00100>) followed by one or more Polo box (PB) motifs (see <PDOC50078>) separated by linkers of varying length. PBs are ~70-80-aa multifunctional domains that serve as hubs of protein interaction and are important for dimerization, substrate binding, intracellular targeting, and autoinhibition of kinase activity. Plk1-3 contain two carboxy-terminal PBs that interact in cis to bind phosphorylated targets, mediate localization, and activate the kinase. Intriguingly, Plk4/Sak is structurally divergent. It contains only a single carboxy-terminal PB, which confers homodimerization and moderate centriole localization. Plk4 also contains a conserved central domain, called the "cryptic polo box" (CPB), which bridges the kinase domain and the carboxy-terminal PB. The CPB comprises two structurally unique PB domains, CPB1 and CPB2, though it shows no apparent sequence homology to canonical PBs. Both CPB1 and CPB2 adopt a canonical PB fold, delineated by an N-terminal helix that runs diagonal to the β strands (see <PDB:4G7N>) [1,2,3,4].

Plk4 is the master regulator of centriole duplication, and its hyperactivation drives centriole amplification, a phenomenon observed in cancer. Plk4s target mother centrioles through an interaction between their CPB and acidic regions in the centriolar receptors SPD-2/Cep192 and/or Asterless/Cep152 [1,2,3,4].

The profiles we developed cover the entire CPB1 and CPB2 domains.

Last update:

September 2021 / First entry.

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Technical section

PROSITE methods (with tools and information) covered by this documentation:

CPB1, PS51984; Cryptic Polo-Box 1 (CPB1) domain profile  (MATRIX)

CPB2, PS51985; Cryptic Polo-Box 2 (CPB2) domain profile  (MATRIX)


References

1AuthorsElia A.E.H. Rellos P. Haire L.F. Chao J.W. Ivins F.J. Hoepker K. Mohammad D. Cantley L.C. Smerdon S.J. Yaffe M.B.
TitleThe molecular basis for phosphodependent substrate targeting and regulation of Plks by the Polo-box domain.
SourceCell 115:83-95(2003).
PubMed ID14532005
DOI10.1016/s0092-8674(03)00725-6

2AuthorsSlevin L.K. Nye J. Pinkerton D.C. Buster D.W. Rogers G.C. Slep K.C.
TitleThe structure of the plk4 cryptic polo box reveals two tandem polo boxes required for centriole duplication.
SourceStructure 20:1905-1917(2012).
PubMed ID23000383
DOI10.1016/j.str.2012.08.025

3AuthorsShimanovskaya E. Viscardi V. Lesigang J. Lettman M.M. Qiao R. Svergun D.I. Round A. Oegema K. Dong G.
TitleStructure of the C. elegans ZYG-1 cryptic polo box suggests a conserved mechanism for centriolar docking of Plk4 kinases.
SourceStructure 22:1090-1104(2014).
PubMed ID24980795
DOI10.1016/j.str.2014.05.009

4AuthorsKlebba J.E. Buster D.W. McLamarrah T.A. Rusan N.M. Rogers G.C.
TitleAutoinhibition and relief mechanism for Polo-like kinase 4.
SourceProc. Natl. Acad. Sci. U. S. A. 112:E657-E666(2015).
PubMed ID25646492
DOI10.1073/pnas.1417967112



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