Polo-like kinases (Plks) belong to the serine/threonine kinase subfamily, and are characterized by the presence of the signature motif called Polo-box domain. Plks are key regulators of cell cycle and cell division in eukaryotes [, ]. Unicellular organisms contain one Plk whereas higher eukaryotes have as many as four Plks: Plk1, Plk2, Plk3 andPlk4.Plk4 (also called Sak) is the most structurally divergent member of the Plks. It plays a pivotal role in centriole duplication [, , , , ]and is required for centriolar satellite function and ciliogenesis []. Substrates identified for Plk4 include Cdc25C and Chk2 [, ].
14-3-3 tau/theta (tau in humans, theta in mice) isoform is encoded by the YWHAQ gene in humans and plays an important role in controlling apoptosis through interactions with ASK1, c-jun NH-terminal kinase, and p38 mitogen-activated protein kinase (MAPK). Its interaction with CDC25c regulates entry into the cell cycle and subsequent interaction with Bad prevents apoptosis. 14-3-3 theta protein expression is induced in patients with amyotrophic lateral sclerosis []. 14-3-3 tau is often overexpressed in breast cancer, which is associated with the downregulation of p21, a p53 target gene, and thus leads to tamoxifen resistance in MCF7 breast cancer cells and shorter patientsurvival. Therefore, 14-3-3 tau may be a potential therapeutic target in breast cancer []. Additionally, 14-3-3 theta mediates nucleocytoplasmic shuttling of the coronavirus nucleocapsid protein which causes severe acute respiratory syndrome []. 14-3-3 domain is an essential part of 14-3-3 proteins, a ubiquitous class of regulatory, phosphoserine/threonine-binding proteins found in all eukaryotic cells, including yeast, protozoa and mammalian cells [].
A subgroup of serine/threonine protein kinases, Polo or Polo-like kinases play multiple roles during the cell cycle. Polo kinases are required at several key points through mitosis, starting from control of the G2/M transition through phosphorylation of Cdc25C and mitotic cyclins. They are also involved in meiosis I as regulators of kinetochore function [, ]. Polo kinases are characterised by an amino terminal catalytic domain, and a carboxy terminal non-catalytic domain consisting of three blocks of conservedsequences known as polo boxes which form one single functional domain []. The domain is named after its founding member encoded by the polo gene of Drosophila melanogaster []. This domain of around 70 amino acids has been found in species ranging from yeast to mammals. Polo boxes appear to mediate interaction with multiple proteins through protein:protein interactions; some but not all of these proteins are substrates for the kinase domain of the molecule [].The crystal structure of the polo domain of the murine protein, Sak, is dimeric, consisting of two α-helices and two six-stranded β-sheets []. The topology of one polypeptide subunit of the dimer consists of, from its N- to C terminus, an extended strand segment, five β-strands, one α-helix (A) and C-terminal β-strand. β-strands from one subunit form a contiguous antiparallel β-sheet with β-strands from the second subunit. The two β-sheets pack with crossing angle of 110 degrees, orienting the hydrophobic surfaces inward and the hydrophilic surfaces outward. Helix A, which is colinear with β-strand 6 of the same polypeptide, buries a large portion of the non-overlapping hydrophobic β-sheet surfaces. Interactions involving helices A comprise a majority of the hydrophobic core structure and also the dimer interface.Point mutations in the Polo box of the budding yeast Cdc5 protein abolish the ability of overexpressed Cdc5 to interact with the spindle poles and to organise cytokinetic structures [].
A subgroup of serine/threonine protein kinases, Polo or Polo-like kinases play multiple roles during the cell cycle. Polo kinases are required at several key points through mitosis, starting from control of the G2/M transition through phosphorylation of Cdc25C and mitotic cyclins. They are also involved in meiosis I as regulators of kinetochore function [, ]. Polo kinases are characterised by an amino terminal catalytic domain, and a carboxy terminal non-catalytic domain consisting of three blocks of conservedsequences known as polo boxes which form one single functional domain []. The domain is named after its founding member encoded by the polo gene of Drosophila melanogaster []. This domain of around 70 amino acids has been found in species ranging from yeast to mammals. Polo boxes appear to mediate interaction with multiple proteins through protein:protein interactions; some but not all of these proteins are substrates for the kinase domain of the molecule [].The crystal structure of the polo domain of the murine protein, Sak, is dimeric, consisting of two α-helices and two six-stranded β-sheets []. The topology of one polypeptide subunit of the dimer consists of, from its N- to C terminus, an extended strand segment, five β-strands, one α-helix (A) and C-terminal β-strand. β-strands from one subunit form a contiguous antiparallel β-sheet with β-strands from the second subunit. The two β-sheets pack with crossing angle of 110 degrees, orienting the hydrophobic surfaces inward and the hydrophilic surfaces outward. Helix A, which is colinear with β-strand 6 of the same polypeptide, buries a large portion of the non-overlapping hydrophobic β-sheet surfaces. Interactions involving helices A comprise a majority of the hydrophobic core structure and also the dimer interface.Point mutations in the Polo box of the budding yeast Cdc5 protein abolish the ability of overexpressed Cdc5 to interact with the spindle poles and to organise cytokinetic structures [].
