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Review
. 2021 Nov 18;22(22):12445.
doi: 10.3390/ijms222212445.

Beyond HAT Adaptor: TRRAP Liaisons with Sp1-Mediated Transcription

Bo-Kun Yin  1 , Zhao-Qi Wang  1   2
Affiliations
Review

Beyond HAT Adaptor: TRRAP Liaisons with Sp1-Mediated Transcription

Bo-Kun Yin et al. Int J Mol Sci. .

Abstract

The members of the phosphatidylinositol 3-kinase-related kinase (PIKK) family play vital roles in multiple biological processes, including DNA damage response, metabolism, cell growth, mRNA decay, and transcription. TRRAP, as the only member lacking the enzymatic activity in this family, is an adaptor protein for several histone acetyltransferase (HAT) complexes and a scaffold protein for multiple transcription factors. TRRAP has been demonstrated to regulate various cellular functions in cell cycle progression, cell stemness maintenance and differentiation, as well as neural homeostasis. TRRAP is known to be an important orchestrator of many molecular machineries in gene transcription by modulating the activity of some key transcription factors, including E2F1, c-Myc, p53, and recently, Sp1. This review summarizes the biological and biochemical studies on the action mode of TRRAP together with the transcription factors, focusing on how TRRAP-HAT mediates the transactivation of Sp1-governing biological processes, including neurodegeneration.

Keywords: HAT; Sp1; TRRAP; neuodegeneration; neuro-development; transcription.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Protein domains of the phosphatidylinositol 3-kinase-related kinase (PIKK) family members. All members contain the PIK-like domain that confers kinase activity, except TRRAP that lacks the key motifs (marked with asterisk). The PIK-like domain is flanked by the FAT domain and the FATC domain. PIK3C3, a member of phosphoinositide 3-kinases (PI3K), serves as a comparison. The known regions (blue numbers) in TRRAP, which interact with p53, c-Myc, and LXR (liver X receptor), are shown. Many of the proteins have been reported to associate with TRRAP; however, if there are no exact regions mapped, these proteins are not shown. The black numbers indicate the amino acid sequence of TRRAP. All of the proteins were aligned with the dashed line, which indicates the N-terminal border of the PIK-like/PIK domain. PIKK, phosphatidylinositol 3-kinase-related kinase; PI3K, phosphoinositide 3-kinases; PIK3C3, phosphatidylinositol 3-kinase catalytic subunit type 3.
Figure 2
Figure 2
Protein structure of Sp1 with indicated domains and post-translational modifications. Domains A, B, C, and D indicate transactivation domains. All of the other domains are indicated in boxes with different colors. Putative post-translational modifications are labelled in color-coded circles. The numbers under the protein indicate the position of the amino acid at the border of the domains. S/T-rich: serine/threonine-rich domain; Q-Rich: glutamine-rich domain; BTD: Buttonhead domain; Zn finger: Cys2His2-type zinc finger domain. UniProt ID: P08047 and references [46,47,48].
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