{PDOC51984}
{PS51984; CPB1}
{PS51985; CPB2}
{BEGIN}
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* Cryptic Polo-Box 1 and 2 (CPB1 and CPB2) domains profiles *
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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 (Plk1–4) 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 beta 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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: September 2021 / First entry.

[ 1] Elia 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.
     "The molecular basis for phosphodependent substrate targeting and
     regulation of Plks by the Polo-box domain."
     Cell 115:83-95(2003).
     PubMed=14532005; DOI=10.1016/s0092-8674(03)00725-6
[ 2] Slevin L.K., Nye J., Pinkerton D.C., Buster D.W., Rogers G.C.,
     Slep K.C.
     "The structure of the plk4 cryptic polo box reveals two tandem polo
     boxes required for centriole duplication."
     Structure 20:1905-1917(2012).
     PubMed=23000383; DOI=10.1016/j.str.2012.08.025
[ 3] Shimanovskaya E., Viscardi V., Lesigang J., Lettman M.M., Qiao R.,
     Svergun D.I., Round A., Oegema K., Dong G.
     "Structure of the C. elegans ZYG-1 cryptic polo box suggests a
     conserved mechanism for centriolar docking of Plk4 kinases."
     Structure 22:1090-1104(2014).
     PubMed=24980795; DOI=10.1016/j.str.2014.05.009
[ 4] Klebba J.E., Buster D.W., McLamarrah T.A., Rusan N.M., Rogers G.C.
     "Autoinhibition and relief mechanism for Polo-like kinase 4."
     Proc. Natl. Acad. Sci. U. S. A. 112:E657-E666(2015).
     PubMed=25646492; DOI=10.1073/pnas.1417967112

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