Reactome | SIRT1 deacetylates HINT1 dimer

SIRT1 deacetylates HINT1 dimer

Stable Identifier

R-HSA-9825772

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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HINT1 is a transcriptional repressor protein with tumor suppressive activity that exerts its influence by binding to transcription factors like MITF and CTNNB1 (Lee et al, 2004; Razin et al, 1999; Weiske et al, 2005; Genovese et al, 2009). The ability of HINT1 to bind to MITF and CTNNB1 is modulated by its acetylation state at lysine residues K21 and K30 (Choudhary et al, 2009; Motzik et al, 2017). Deacetylation at these sites by SIRT1 promotes the interaction between MITF and HINT1 and consequently restricts the transcription of MITF-dependent target genes (Jung et al, 2020).

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
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