Reactome | TP53INP1 and HIPK2 bind TP53

TP53INP1 and HIPK2 bind TP53

Stable Identifier

R-HSA-3215251

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

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Gene expression (Transcription) (Homo sapiens)

- RNA Polymerase II Transcription (Homo sapiens)
  - Generic Transcription Pathway (Homo sapiens)
    - Transcriptional Regulation by TP53 (Homo sapiens)
      - Regulation of TP53 Activity (Homo sapiens)
        
        Regulation of TP53 Activity through Phosphorylation (Homo sapiens)
        
        TP53INP1 and HIPK2 bind TP53 (Homo sapiens)

General

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TP53INP1 (p53INP1) forms a complex with TP53 and its regulating kinase HIPK2 (Tomasini et al. 2003, Okamura et al. 2001). HIPK2 undergoes autophosphorylation in response to DNA damage, but the mechanism and the identity of autophosphorylation sites have not yet been fully elucidated (Bitomsky et al. 2013, Saul et al. 2013, Siepi et al. 2013). Autophosphorylation enables HIPK2 binding to PIN1. PIN1 likely facilitates a conformational change that enables HIPK2 to phosphorylate its targets, including TP53 (Bitomsky et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
23485397	HIPK2 catalytic activity and subcellular localization are regulated by activation-loop Y354 autophosphorylation Gatti, V, Soddu, S, Siepi, F, Crescenzi, M, Camerini, S	Biochim. Biophys. Acta	2013
12851404	TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity Malissen, B, Tomasini, R, Carrier, A, Dusetti, NJ, Isnardon, D, Samir, AA, Cecchinelli, B, Soddu, S, Iovanna, JL, Dagorn, JC	J. Biol. Chem.	2003
11511362	p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis Arakawa, H, Nakanishi, H, Nakamura, Y, Monden, M, Taya, Y, Ng, CC, Tanaka, T, Okamura, S	Mol. Cell	2001
23000554	HIPK2 kinase activity depends on cis-autophosphorylation of its activation loop de la Vega, L, Schmitz, ML, Fritz-Wolf, K, Braun, T, Becker, K, Saul, VV, Milanovic, M, Krüger, M	J Mol Cell Biol	2013
24145406	Autophosphorylation and Pin1 binding coordinate DNA damage-induced HIPK2 activation and cell death Schultheiss, K, Greiner, V, Sombroek, D, Moritz, C, Glas, C, Peri, F, Del Sal, G, Conrad, E, Polonio-Vallon, T, Hofmann, TG, Mantovani, F, Herbel, C, Bitomsky, N	Proc. Natl. Acad. Sci. U.S.A.	2013