Reactome | CREBBP acetylates HINT1 dimer

CREBBP acetylates HINT1 dimer

Stable Identifier

R-HSA-9825747

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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Histidine Triad Nucleotide-binding protein 1 (HINT1) is a tumor suppressor protein that exerts its function in part by binding to and repressing transcription factors such as MITF and CTNNB1 (beta-catenin) (Razin et al, 1999; Lee et al, 2004; Weiske and Huber, 2005; Genovese et al, 2009). Activity of HINT1 is regulated by post-translational modifications, notably acetylation. CREBBP-dependent acetylation of HINT1 at K21 and K30 disrupts the interaction of HINT1 and MITF, liberating MITF to bind and activate its transcriptional targets (Choudhary et al, 2009; Motzik et al, 2017; Jung et al, 2020; reviewed in Goding and Arnheiter 2019).

Literature References

PubMed ID	Title	Journal	Year
28394346	Post-translational modification of HINT1 mediates activation of MITF transcriptional activity in human melanoma cells Guo, M, Amir, E, Nechushtan, H, Kim, JH, Kim, BG, Erlich, T, Motzik, A, Han, JM, Tshori, S, Wang, J, Razin, E	Oncogene	2017
19608861	Lysine acetylation targets protein complexes and co-regulates major cellular functions Rehman, M, Nielsen, ML, Olsen, JV, Walther, TC, Choudhary, C, Kumar, C, Gnad, F, Mann, M	Science	2009
14975237	The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells Lee, YN, Razin, E, Nechushtan, H, Figov, N	Immunity	2004
16014379	The histidine triad protein Hint1 interacts with Pontin and Reptin and inhibits TCF-beta-catenin-mediated transcription Huber, O, Weiske, J	J Cell Sci	2005
31123060	MITF-the first 25 years Arnheiter, H, Goding, CR	Genes Dev	2019
32636443	Deacetylation by SIRT1 promotes the tumor-suppressive activity of HINT1 by enhancing its binding capacity for β-catenin or MITF in colon cancer and melanoma cells Jin, GR, Jung, TY, Lee, SY, Ju, BG, Jang, MM, Kim, H, Lee, CY, Lee, SY, Koo, YB, Kim, HS, Kim, CW	Exp Mol Med	2020
10567402	Suppression of microphthalmia transcriptional activity by its association with protein kinase C-interacting protein 1 in mast cells Rivera, J, Nechushtan, H, Frenkel, S, Zhang, ZC, Lee, YN, Arudchandran, R, Razin, E	J Biol Chem	1999
22647378	The tumor suppressor HINT1 regulates MITF and β-catenin transcriptional activity in melanoma cells Sioletic, S, Sgambato, A, Cittadini, A, Rettino, A, Ghosh, P, Genovese, G, Li, H	Cell Cycle	2012