Reactome | PHF6 binds NuRD

PHF6 binds NuRD

Stable Identifier

R-HSA-9941744

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

3/5

Locations in the PathwayBrowser

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Chromatin organization (Homo sapiens)

- ATP-dependent chromatin remodelers (Homo sapiens)
  - CHD chromatin remodelers (Homo sapiens)
    - CHD3, CHD4, CHD5 subfamily (Homo sapiens)
      - NuRD complex assembly (Homo sapiens)
        
        Interaction of NuRD complexes with transcription factors (Homo sapiens)
        
        PHF6 binds NuRD (Homo sapiens)

General

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PHF6 (Plant homeodomain finger 6) is an incompletely characterized C4HC3 zinc-finger-containing protein that has been shown to interact with components of the NuRD complex including CHD4, CHD3, RBBP4 and HDAC1 (Todd et al, 2012; Liu et al, 2014; Liu et al, 2015). PHF6 has two imperfect zinc finger PHD domains, demonstrated in other proteins to function as chromatin readers and as mediators of protein-protein interactions (reviewed in Guarav and Kutateladze, 2023; Sanchez and Zhou, 2011), however PHF6 appears not to contact histones but rather to interact non-specifically with double-stranded DNA through a positively charged surface (Liu et al, 2014). PHF6 acts as a transcriptional repressor when tethered to a GAL4 DNA-binding domain in a reporter gene assay in HEK293 cells; knockdown of RBBP4 abrogated the transcriptional repression mediated by PHF6 (Liu et al, 2015).
Mutations in PHF6 are associated with the X-linked neurodevelopmental disorder Borjeson-Forssman-Lehman Syndrome as well as with T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) (reviewed in Jahani-Asl et al, 2016; Eisa et al, 2023; Fan et al, 2024).

Literature References

PubMed ID	Title	Journal	Year
36008597	The Role of PHF6 in Hematopoiesis and Hematologic Malignancies Eisa, YA, Guo, Y, Yang, FC	Stem Cell Rev Rep	2023
21514168	The PHD finger: a versatile epigenome reader Sanchez, R, Zhou, MM	Trends Biochem Sci	2011
38813086	Deciphering the dual roles of PHD finger proteins from oncogenic drivers to tumor suppressors Fan, T, Jiang, L, Zhou, X, Chi, H, Zeng, X	Front Cell Dev Biol	2024
24554700	Structural and functional insights into the human Börjeson-Forssman-Lehmann syndrome-associated protein PHF6 Liu, Z, Li, F, Ruan, K, Zhang, J, Mei, Y, Wu, J, Shi, Y	J Biol Chem	2014
25601084	Structural basis of plant homeodomain finger 6 (PHF6) recognition by the retinoblastoma binding protein 4 (RBBP4) component of the nucleosome remodeling and deacetylase (NuRD) complex Liu, Z, Li, F, Zhang, B, Li, S, Wu, J, Shi, Y	J Biol Chem	2015
27633282	Pathogenesis of Börjeson-Forssman-Lehmann syndrome: Insights from PHF6 function Jahani-Asl, A, Cheng, C, Zhang, C, Bonni, A	Neurobiol Dis	2016
22720776	PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex Todd, MA, Picketts, DJ	J Proteome Res	2012
37061424	Non-histone binding functions of PHD fingers Gaurav, N, Kutateladze, TG	Trends Biochem Sci	2023