Literature summary for 2.7.1.105 extracted from

Yalcin, A.; Clem, B.F.; Imbert-Fernandez, Y.; Ozcan, S.C.; Peker, S.; ONeal, J.; Klarer, A.C.; Clem, A.L.; Telang, S.; Chesney, J.
6-Phosphofructo-2-kinase (PFKFB3) promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phosphorylation of p27 (2014), Cell Death Dis., 5, e1337.

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Protein Variants

Protein Variants	Comment	Organism
additional information	siRNA silencing of endogenous PFKFB3 in HeLa cells by siRNA	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one	the PFKFB3 inhibitor, 3PO, increases p27 protein in Lewis lung carcinoma cells in vitro and in vivo	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
nucleus	-	Homo sapiens	5634	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP + beta-D-fructose 6-phosphate	Homo sapiens	-	ADP + beta-D-fructose 2,6-bisphosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q16875	gene PFKFB3	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
HCT-116 cell	PFKFB3 is overexpressed in human cancers	Homo sapiens	-
HeLa cell	-	Homo sapiens	-
HeLa cell	PFKFB3 is overexpressed in human cancers	Homo sapiens	-
Lewis lung carcinoma cell	-	Homo sapiens	-
LLC cell	PFKFB3 is overexpressed in human cancers	Homo sapiens	-
additional information	PFKFB3 is overexpressed in human cancers	Homo sapiens	-
PANC-1 cell	PFKFB3 is overexpressed in human cancers	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + beta-D-fructose 6-phosphate	-	Homo sapiens	ADP + beta-D-fructose 2,6-bisphosphate	-	?

Synonyms

Synonyms	Comment	Organism
6-phosphofructo-2-kinase	-	Homo sapiens
PFKFB3	-	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	siRNA silencing of endogenous PFKFB3 inhibits Cdk1 activity, which in turn stabilizes p27 protein levels causing cell cycle arrest at G1/S and increased apoptosis in HeLa cells. PFKFB3 inhibition completely suppresses cell proliferation and results in increased early and late apoptotic cells. PFKFB3 inhibition results in increased nuclear and cytoplasmic p27 protein but has no effect on p57 or p21. Blockade of cell cycle progression and stimulation of apoptosis by PFKFB3 inhibition is mediated by p27	Homo sapiens
metabolism	the family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) comprises well established regulators of glucose metabolism via their synthesis of fructose-2,6 bisphosphate, a potent allosteric activator of 6-phosphofructo-1-kinase. But PFKFB3 and fructose-2,6 bisphosphate function not only as regulators of Pfk-1 but also of Cdk1 activity, and therefore serve to couple glucose metabolism with cell proliferation and survival in transformed cells	Homo sapiens
physiological function	PFKFB3 is overexpressed in human cancers, regulated by HIF-1alpha, Akt and PTEN, and required for the survival and growth of multiple cancer types. Role of PFKFB3 in regulating Cdk1- and p27-mediated G1/S blockade and apoptosis	Homo sapiens

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Release 2023.1 (January 2023)