Literature summary for 1.14.18.B1 extracted from

Maina, P.K.; Shao, P.; Jia, X.; Liu, Q.; Umesalma, S.; Marin, M.; Long, D.; Concepcion-Roman, S.; Qi, H.H.
Histone demethylase PHF8 regulates hypoxia signaling through HIF1alpha and H3K4me3 (2017), Biochim. Biophys. Acta, 1860, 1002-1012 .

Search for more literature for 1.14.18.B1

Protein Variants

Protein Variants	Comment	Organism
additional information	knockdown or knockout of PHF8 by RNAi or CRISPR-Cas9 system	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.
histone H3 N6,N6-dimethyl-L-lysine27 + 2-oxoglutarate + O2	Homo sapiens	-	histone H3 N6-methyl-L-lysine27 + succinate + formaldehyde + CO2	-	?
additional information	Homo sapiens	enzyme PHF8 binds and stabilizes histone H3 N6,N6,N6-trimethyl-L-lysine4, PHF8 is important in maintaining H3K4me3 levels. PHF8 cooperates with KDM3A	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q9UPP1	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
LNCaP cell	-	Homo sapiens	-
prostate cancer cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
histone H3 N6,N6-dimethyl-L-lysine27 + 2-oxoglutarate + O2	-	Homo sapiens	histone H3 N6-methyl-L-lysine27 + succinate + formaldehyde + CO2	-	?
additional information	enzyme PHF8 binds and stabilizes histone H3 N6,N6,N6-trimethyl-L-lysine4, PHF8 is important in maintaining H3K4me3 levels. PHF8 cooperates with KDM3A	Homo sapiens	?	-	?
additional information	the enzyme also demethylates mono- and dimethylated H3 Lys9 (H3K9Me1/2) and monomethylated histone H4 Lys20 residue (H4K20Me1)	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
histone demethylase	-	Homo sapiens
PHD finger protein 8	-	Homo sapiens
PHF8	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	PHF8 knockout by the CRISPR-Cas9 system attenuates hypoxia signaling in 293T cells. Knockdown or knockout of PHF8 by RNAi or CRISPR-Cas9 system reduces the activation of HIF1alpha and the induction of HIF1alpha target genes including KDM3A. Despite the impaired hypoxia induced stabilization of HIF1alpha protein, the upregulation of KDM3A is only attenuated by PHF8 knockout. PHF8 knockdown elevates H3K9me2 at the 3'UTRs of KDM3A, VEGFA and at the TSS of ENO2 under normoxia. Knockdown of PHF8 increases H3K27me2 at the TSS of ENO2 and decreases H3K27me2 at the 3'UTR of ENO2, respective	Homo sapiens
physiological function	PHF8 regulates hypoxia inducible genes mainly through sustaining the level of trimethylated histone 3 lysine 4 (H3K4me3), an active mark in transcriptional regulation. The positive role of PHF8 in hypoxia signaling extends to hypoxia-induced neuroendocrine differentiation (NED), wherein PHF8 cooperates with KDM3A to regulate the expression of NED genes. The role of PHF8 in hypoxia signaling is associated with the presence of full-length androgen receptor in CRPC cells. PHF8 is an epigenetic factor in hypoxia signaling, and the underlying regulatory mechanisms likely apply to general cancer development involving HIF1alpha. PHF8 regulates hypoxia inducible genes mainly through sustaining the level of trimethylated histone 3 lysine 4 (H3K4me3), an active mark in transcriptional regulation. PHF8 (PHD finger protein 8) is dynamically regulated during the neuroendocrine differentiation that occurs in prostate cancer, and that the c-MYC-miR-22 axis contributes to the regulation of PHF8 in the context of androgen depletion and interleukin-6 treatment. PHF8 plays a critical role in hypoxia signaling as it positively regulates KDM3A which is a critical coactivator of key transcription factor hypoxia-inducible factor 1-alpha, HIF1alpha, indirectly sustains H3K4me3 levels on select hypoxia-inducible genes, and is required for full activation of HIF1alpha through various mechanisms. In the context of prostate cancer, PHF8 appears to execute its regulatory function during hypoxia signaling in androgen receptor-positive prostate cancer cells	Homo sapiens

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Release 2023.1 (January 2023)