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Table 1 List of TIP60 PTM sites, catalyzing enzymes and their implications on TIP60-associated functions

From: Post-translational modifications of epigenetic modifier TIP60: their role in cellular functions and cancer

Site

Modifying Enzyme

Eraser Enzyme

Function

Reference

Ser 86 Phosphorylation

GSK3 β

 

HAT activity of TIP60, cell cycle regulation & progression, chromosomal segregation, autophagy, apoptosis, DSB repair, and TAG (triacyl glycerol) synthesis

[19, 47, 48, 49, 55]

Ser 90 Phosphorylation

Cyclin B/ cdc2, CDK9

 

HAT activity of TIP60, cell cycle regulation & progression, chromosomal segregation, association with H3 and RNA pol II.

[24, 48, 57]

Thr 158 phosphorylation

p38α, VRK1

 

Apoptosis, DNA damage response, TIP60 autoacetylation, oncogene-induced senescence, chromatin loading

[59, 60, 62]

Ser 199 phosphorylation

DNA-PK

 

TIP60 autoacetylation, DNA damage response

[60]

Tyr 294 phosphorylation

Ab1

 

HAT activity, protein localization, cell cycle regulation, interaction with Fe65

[63]

Lys 104 acetylation

TIP60 (auto-acetylation)

 

Apoptosis, NuA4 complex partner interaction

[84]

Lys 104, Lys 120, Lys 148, Lys 150, Lys 187, and Lys 189 acetylation

TIP60 (auto-acetylation)

HDAC3, SIRT1

Apoptosis

[83]

Lys 187 acetylation

TIP60 (auto-acetylation)

 

Nuclear localization, phase separation, HAT activity, DNA damage repair, and wound healing

[29]

Lys 327 acetylation

TIP60 (auto-acetylation), p300

 

HAT & autoacetylation activity, FOXP3 transcriptional activity

[82, 85]

Lys 268 and Lys 282 acetylation

p300/CBP

 

Function not known

[86]

Lys 189 Methylation

SET7

LSD1

DNA double strand break repair, Colon cancer cell proliferation

[99]

Lys 430 SUMOylation

PIASγ, Ubc9

SENP3

DNA damage repair, Autophagy

[92, 93, 94, 95]

Lys 451 SUMOylation

PIASγ, Ubc9

 

DNA damage repair, Autophagy

[92, 93]

Ser 119 O-GlcNAc

(OGT) O-linked N-acetylglucosaminyltransferase

 

TIP60 stabilization, upregulation of MMP9 & 14 (c-myc mediated), Metastasis (TWIST1 mediated)

[104]

Asn 291 N-glycosylation

  

TIP60 stability, subcellular localization, HAT activity, interaction with Fe65

[103]

Ubiquitination (sites not known)

MDM2

 

TIP60 degradation, protein turnover

[111]

Ubiquitination (sites not known)

UHRF1

 

TIP60 stability, tumor suppression

[112]

Ubiquitination (sites not known)

 

USP7

Apoptosis

[113]

Lys35, Lys150, Lys243, Lys359, Lys296, and Lys404 Ubiquitination

 

USP7

Regulates adipogenesis

[114]