Literature summary for 2.7.11.21 extracted from

Xiao, D.; Yue, M.; Su, H.; Ren, P.; Jiang, J.; Li, F.; Hu, Y.; Du, H.; Liu, H.; Qing, G.
Polo-like kinase-1 regulates Myc stabilization and activates a feedforward circuit promoting tumor cell survival (2016), Mol. Cell, 64, 493-506.

Search for more literature for 2.7.11.21

Application

Application	Comment	Organism
pharmacology	combined inhibition of PLK1 and Bcl2 represent potential Myc-targeting therapeutics	Homo sapiens

Cloned(Commentary)

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

Protein Variants	Comment	Organism
additional information	PLK1 shRNA knockdown	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
BI2536	-	Homo sapiens
BI6727	-	Homo sapiens
GSK461364	-	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism	UniProt	Comment	Textmining
Homo sapiens	P53350	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
neuroblastoma cell	-	Homo sapiens	-

Substrates and Products (Substrate)

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

Synonyms	Comment	Organism
Plk1	-	Homo sapiens
polo-like kinase-1	-	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Homo sapiens

Expression

Organism	Comment	Expression
Homo sapiens	N-Myc directly activates PLK1 transcription	up

General Information

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

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Release 2023.1 (January 2023)