PLK1, a protein kinase, plays various roles in different cellular processes and pathways

NCBI ID: G5347

PLK1

PLK1, a protein kinase, plays various roles in different cellular processes and pathways

In the cell cycle progression, PLK1 phosphorylates and translocates GTSE1 into the nucleus, which then binds to p53 and shuttles it from the nucleus to the cytoplasm. This leads to the inactivation of p53 and checkpoint recovery.

PLK1 also interacts with Smad-3 and stabilizes HEF1, allowing it to interact with Aur-A. This interaction is essential for the disassembly of primary cilia before mitosis. In the absence of PLK1, Smad-3 generates a HEF1 destruction complex, leading to the degradation of HEF1 and preventing its interaction with Aur-A in the G0/G1 phase.

Up-regulated PLK1 inhibits the damage repair mechanism and releases cells from G2/M arrest with damaged DNA. It phosphorylates and degrades several proteins associated with DNA repair and G2/M arrest, such as Chk-2, p53, MYT1, WEE1, and claspin. PLK1's phosphorylation of RAD51 activates BRCA1/2 and recruits the RAD51-NBS complex to repair DNA damage. Additionally, PLK1 phosphorylation blocks the G1/S transition, providing time for damage repair.

In pancreatic cancer, a combination therapy involving a small molecule PLK1 inhibitor and microRNA-34a is illustrated as a potential treatment option.

PLK1 is also involved in regulating chromosome condensation, MTOC fragmentation, and LISD recruitment in mammalian oocytes. It dissociates C-NAP1, allowing MTOC components to fragment and form bipolar spindles. PLK1 is required for the recruitment of Aurora A and TACC3 in oocytes. The absence of PLK1 leads to defects in chromosome condensation, MTOC failure, and abnormal spindle formation in oocytes.

These viewpoints highlight the diverse functions of PLK1 in different cellular pathways, including cell cycle regulation, DNA damage response, cancer treatment, and reproductive processes.
Based on the provided context information, here are some key viewpoints regarding PLK1:

PLK1 plays a role in substrate recognition and mitotic progression.
PLK1 has two classes of phospho-substrates: one including proteins 'X' and 'Y' (e.g., NEDD1) and the other containing a hydrophobic amino acid residue near the pS/pT residue, such as protein 'P' (e.g., PBIP1).
PLK1Wt (wild type) can bind to both categories of PBD-substrates.
PLK1AAD does not bind to protein 'P'-like substrates.
PLK1AM does not bind to any substrates.
Following mitochondrial depolarization, PINK accumulates on the outer mitochondrial membrane and recruits Parkin from the cytosol. The activation of Parkin on Ser 65 by PINK enables the formation of ubiquitin chains, leading to the recruitment of the autophagic machinery.
Damaged mitochondria are engulfed by autophagosomes, which later fuse with lysosomes to form autophagolysosomes.
During cell division, PLK1 activates Parkin, allowing it to bind to Cdc20 or Cdh1 and facilitate the destruction of substrates controlled by these two APC/C activators.

These viewpoints cover various aspects of PLK1's function in mitotic progression, its role in substrate recognition, and its involvement in mitochondrial health and cell division.

Protein Name: Polo Like Kinase 1

Functions: Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis. Polo-like kinase proteins acts by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, PPP1R12A/MYPT1, PRC1, RACGAP1/CYK4, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU. Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL. NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins. Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1. Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains. Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation. Promotes the central spindle recruitment of ECT2. Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1. Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1. Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase. Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity. Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2. PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation. Required for kinetochore localization of BUB1B. Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2. Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function. Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome. Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53. Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA. Contributes to the regulation of AURKA function. Also required for recovery after DNA damage checkpoint and entry into mitosis. Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (PubMed:8991084, PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (By similarity). Phosphorylates CEP68 and is required for its degradation (PubMed:25503564). Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (PubMed:20679239). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitm

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