Application | Comment | Organism |
---|---|---|
pharmacology | combined inhibition of PLK1 and Bcl2 represent potential Myc-targeting therapeutics | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
recombinant co-expression of Myc-tagged Fbw7 with PLK1 in HEK-293T cells, and expressed full-length PLK1 in combination with FLAG-tagged Fbw7 or truncation mutants | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | PLK1 shRNA knockdown | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
BI2536 | - |
Homo sapiens | |
BI6727 | - |
Homo sapiens | |
GSK461364 | - |
Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + SCFFbw7 ubiquitin ligase | Homo sapiens | - |
ADP + phosphorylated SCFFbw7 ubiquitin ligase | - |
? | |
additional information | Homo sapiens | selective association between PLK1 and Fbw7 proteins. The WD40 domain of Fbw7 interacts with PLK1 as strongly as the full-length protein, the WD40 domain is responsible for Fbw7 association with PLK1, and the C-terminal Polobox domain (PBD), but not the N-terminal kinase domain (KD), within PLK1 selectively interacts with Fbw7 WD40 domain | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P53350 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
neuroblastoma cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + SCFFbw7 ubiquitin ligase | - |
Homo sapiens | ADP + phosphorylated SCFFbw7 ubiquitin ligase | - |
? | |
additional information | selective association between PLK1 and Fbw7 proteins. The WD40 domain of Fbw7 interacts with PLK1 as strongly as the full-length protein, the WD40 domain is responsible for Fbw7 association with PLK1, and the C-terminal Polobox domain (PBD), but not the N-terminal kinase domain (KD), within PLK1 selectively interacts with Fbw7 WD40 domain | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
Plk1 | - |
Homo sapiens |
polo-like kinase-1 | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens |
Organism | Comment | Expression |
---|---|---|
Homo sapiens | N-Myc directly activates PLK1 transcription | up |
General Information | Comment | Organism |
---|---|---|
malfunction | combination treatment with PLK1 and Bcl2 pharmacological inhibitors specifically induces synergistic cell death, partly because of PLK1 inhibitor-mediated depletion of Myc and Mcl1 expression | Homo sapiens |
physiological function | PLK1 promotes Fbw7 phosphorylation, selfubiquitination, and proteasomal degradation, creating a PLK1-Myc feedforward activation loop in MYC overexpressing tumor cells. PLK1 specifically binds to the SCFFbw7 ubiquitin ligase, phosphorylates it, and promotes its autopolyubiquitination and proteasomal degradation, counteracting Fbw7-mediated degradation of N-Myc and additional substrates, including cyclin E and Mcl1. Stabilized N-Myc in turn directly activates PLK1 transcription, constituting a positive feedforward regulatory loop that reinforces Myc-regulated oncogenic programs, association between Myc deregulation and PLK1 dependence. Analysis of the molecular mechanism responsible for reciprocal activation between Polo-like kinase-1 and N-Myc, PLK1-Fbw7-Myc signaling circuit, overview. PLK1 Reduces Fbw7 stability through promotion of its phosphorylation and autopolyubiquitination, Fbw7 turnover is mediated by autocatalytic ubiquitin transfer | Homo sapiens |