TIP60 acts as a regulator of genes involved in filopodia formation and cell migration during wound healing

Dubey, Shraddha; Jaiswal, Bharti; Gupta, Ashish

doi:10.1016/j.jbc.2022.102015

Cited by 7 publications

(10 citation statements)

References 62 publications

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“…For example, we found that the chromatin binding ability of the TIP60 (HAT mutant) (with impaired catalytic activity) is significantly reduced which may be a major reason for the failure of TIP60 HAT mutant to form nuclear puncta 31 , which now we know are formed due to its phase separation. Similarly, we have recently shown that chromodomain mutant of TIP60 that severely loses its chromatin binding ability fails to form nuclear puncta 25 . These results clearly show us that the interplay of the different domains of TIP60 contributes to TIP60's phase separation and TIP60's chromatin binding is a pre-requisite step for its phase separation.…”

Section: Discussionmentioning

confidence: 65%

“…Histone acetyl transferase and autoacetylation assays were performed as mentioned previously 25 . In brief, in vitro HAT assay reaction was setup in HAT buffer added with purified recombinant proteins [(His-TIP60 (Wild-type) or His-TIP60 (K187R)], 0.5 µg histone H4 peptides (Millipore, USA) and 100 µM acetyl-CoA.…”

Section: Star Methodsmentioning

confidence: 99%

“…For obtaining subcellular fractions, we followed the protocol mentioned elsewhere 25 . Transfected cells were trypsinized and washed once with complete DMEM and twice with 1 X PBS, followed by solubilization using solubilisation buffer (10 mM HEPES pH-7.4, 10 mM KCl, 0.05% NP-40, 0.2 mM MgCl 2 , 1% Triton X 100, 100 mM NaCl, 1X protease inhibitor cocktail) for 20 minutes at 4 .…”

Section: Subcellular Fractionation Assaymentioning

confidence: 99%

“…Recently, we have demonstrated the involvement of TIP60 along with PXR in promoting wound healing by modulating the actin reorganization and filopodia formation 25 . TIP60 protein comprise of two characteristic domains common to members of MYST family of HAT proteins: an NH 2 -terminal chromodomain and a highly conserved MYST domain accountable for its catalytic activity.…”

Section: Introductionmentioning

confidence: 99%

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Autoacetylation-mediated phase separation of TIP60 is critical for its functions

Dubey¹,

Gupta²,

Gupta³

2023

Preprint

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TIP60 is an important lysine acetyl transferase protein that participates in various essential cellular activities by catalyzing the post-translational acetylation of lysine residues on histones and various non-histone protein substrates. TIP60 typically localizes to the nucleus in a punctate foci pattern, although defining factors and mechanisms regulating the assembly of TIP60 foci and their spatial distribution inside the nucleus are not understood. In the present study, we report that TIP60 can undergo phase separation to form liquid like droplets in the nuclear compartment, which is facilitated by the presence of an intrinsically disordered region (IDR) located between its chromodomain and catalytic domain. Importantly, we identified that autoacetylation on lysine 187, located within the IDR region of TIP60, is important for nuclear localization, oligomer formation and phase separation. Finally, we observed that the phase separation of TIP60 promotes its interaction with its partner proteins and actively contribute to its cellular functions.

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Section: Discussionmentioning

confidence: 65%

Section: Star Methodsmentioning

confidence: 99%

Section: Subcellular Fractionation Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Autoacetylation-mediated phase separation of TIP60 is critical for its functions

Dubey¹,

Gupta²,

Gupta³

2023

Preprint

Self Cite

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“…Subsequent studies showed that TIP60 is an important part of the multisubunit complex of 18 proteins, which have been found to possess other enzymatic properties including HAT, ATPase, DNA helicase, and DNA binding activities (78,79). TIP60 has been shown to have a role in many important biological processes, including DNA damage repair, chromatin remodeling, transcriptional regulation, cell cycle progression, apoptosis, wound healing, and nuclear receptor signaling (79)(80)(81). In addition to acetylating histones, TIP60 can also acetylate a wide range of non-histone target substrates, including p53, ATM, c-Myc, STAT3, NF-kB, CREB, E2F1 and many nuclear receptors (79,82).…”

Section: Tip60 (Hiv-tat Interactive Protein 60kda/kat5)mentioning

confidence: 99%

Lysine Acetyltransferases and Their Role in AR Signaling and Prostate Cancer

Jaiswal

Agarwal²,

Gupta³

2022

Front. Endocrinol.

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The development and growth of a normal prostate gland, as well as its physiological functions, are regulated by the actions of androgens through androgen receptor (AR) signaling which drives multiple cellular processes including transcription, cellular proliferation, and apoptosis in prostate cells. Post-translational regulation of AR plays a vital role in directing its cellular activities via modulating its stability, nuclear localization, and transcriptional activity. Among various post-translational modifications (PTMs), acetylation is an essential PTM recognized in AR and is governed by the regulated actions of acetyltransferases and deacetyltransferases. Acetylation of AR has been identified as a critical step for its activation and depending on the site of acetylation, the intracellular dynamics and activity of the AR can be modulated. Various acetyltransferases such as CBP, p300, PCAF, TIP60, and ARD1 that are known to acetylate AR, may directly coactivate the AR transcriptional function or help to recruit additional coactivators to functionally regulate the transcriptional activity of the AR. Aberrant expression of acetyltransferases and their deregulated activities have been found to interfere with AR signaling and play a key role in development and progression of prostatic diseases, including prostate cancer (PCa). In this review, we summarized recent research advances aimed at understanding the role of various lysine acetyltransferases (KATs) in the regulation of AR activity at the level of post-translational modifications in normal prostate physiology, as well as in development and progression of PCa. Considering the critical importance of KATs in modulating AR activity in physiological and patho-physiological context, we further discussed the potential of targeting these enzymes as a therapeutic option to treat AR-related pathology in combination with hormonal therapy.

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Experience-dependent Tip60 nucleocytoplasmic transport is regulated by its NLS/NES sequences for neuroplasticity gene control

Armour,

Thomas,

Greco

et al. 2023

Molecular and Cellular Neuroscience

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TIP60 acts as a regulator of genes involved in filopodia formation and cell migration during wound healing

Cited by 7 publications

References 62 publications

Autoacetylation-mediated phase separation of TIP60 is critical for its functions

Autoacetylation-mediated phase separation of TIP60 is critical for its functions

Lysine Acetyltransferases and Their Role in AR Signaling and Prostate Cancer

Experience-dependent Tip60 nucleocytoplasmic transport is regulated by its NLS/NES sequences for neuroplasticity gene control

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