Reactome | Initiation of SAHF formation

Initiation of SAHF formation

Stable Identifier

R-HSA-3878123

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

The evolutionarily conserved complex of HIRA, ASF1A, UBN1 and CABIN1 plays a key role in the formation of senescence-associated heterochromatin foci (SAHF) (Zhang et al. 2005, Banumathy et al. 2009, Rai et al. 2011). Components of this complex, along with other proteins involved in SAHF, accumulate in PML bodies of pre-senescent cells, and relocate to SAHF in senescent cells, with SAHF relocation depending on the functional RB1 and TP53 pathways (Zhang et al. 2005, Ye et al. 2007, Zhang et al. 2007). HIRA serves as a scaffold of HIRA:ASF1A:UBN1:CABIN1 complex, since three different HIRA protein domains interact with ASF1A, UBN1 and CABIN1 (Zhang et al. 2005, Banumathy et al. 2009, Rai et al. 2011). One of the functions of HIRA:ASF1A:UBN1:CABIN1 complex is to deposit histone H3.3 variant onto chromatin, which is dependent on the ASF1A-mediated binding of histone H3, and is involved in the modulation of gene expression in senescent cells (Zhang et al. 2007, Rai et al. 2011).

Literature References

PubMed ID	Title	Journal	Year
15621527	Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA Erzberger, JP, Ye, X, Poustovoitov, MV, Adams, PD, Dunbrack, RL, Santos, HA, Pehrson, JR, Kaufman, PD, Serebriiskii, IG, Chen, W, Daganzo, SM, Zhang, R, Canutescu, AA, Berger, JM	Dev. Cell	2005
17242198	Definition of pRB- and p53-dependent and -independent steps in HIRA/ASF1a-mediated formation of senescence-associated heterochromatin foci Ye, X, Somaiah, N, Zhang, R, Zerlanko, B, Salomoni, P, Adams, PD, Lipinski, M	Mol. Cell. Biol.	2007
21807893	Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a histone H3.3 chaperone complex van Tuyn, J, Rai, TS, McBryan, T, Puri, A, Hoffman, J, Marmorstein, R, Schultz, DC, Adams, PD, Tang, Y, Pchelintsev, NA	Mol. Cell. Biol.	2011
17242207	Molecular dissection of formation of senescence-associated heterochromatin foci Chen, W, Zhang, R, Adams, PD	Mol. Cell. Biol.	2007
19029251	Human UBN1 is an ortholog of yeast Hpc2p and has an essential role in the HIRA/ASF1a chromatin-remodeling pathway in senescent cells Andrake, M, Schultz, D, Zhang, R, Somaiah, N, Banumathy, G, Marmorstein, R, Adams, PD, Ceulemans, H, Tang, Y, Hoffmann, J	Mol. Cell. Biol.	2009