TRRAP, also known as transformation/transcription domain-associated protein, is a unique member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family. Lacking enzymatic activity, it serves as an adaptor protein for histone acetyltransferase (HAT) complexes and a scaffold for multiple transcription factors. TRRAP is involved in diverse biological processes such as cell cycle progression, cell stemness maintenance and differentiation, and neural homeostasis, playing a crucial role in gene transcription by modulating key transcription factors [1].

In mouse models, Trrap deletion compromises self-renewal and differentiation of adult neural stem cells (aNSCs), indicating its importance in adult neurogenesis [2]. In zebrafish, trrap gene-knockout leads to smaller eyes, heads, reduced ventral pharyngeal arches, and impaired tooth mineralization, suggesting its role in craniofacial development [4]. Knockdown or knockout of TRRAP in zebrafish also causes significant defects in the inner ear, showing its importance in inner ear development [5]. In cancer, TRRAP knockdown in colon and ovarian cancer cells reduces tumorigenic potential, spheroid-forming ability, and cisplatin resistance, highlighting its role in cancer stem cell characteristics [3,6].

In conclusion, TRRAP is essential for multiple biological functions including neurogenesis, craniofacial and inner ear development, and cancer-related processes. The use of gene knockout models in mice and zebrafish has significantly contributed to understanding TRRAP's role in these processes, providing insights into potential disease mechanisms and therapeutic targets.

References:

1. Yin, Bo-Kun, Wang, Zhao-Qi. 2021. Beyond HAT Adaptor: TRRAP Liaisons with Sp1-Mediated Transcription. In International journal of molecular sciences, 22, . doi:10.3390/ijms222212445. https://pubmed.ncbi.nlm.nih.gov/34830324/

2. Yin, Bo-Kun, Lázaro, David, Wang, Zhao-Qi. 2022. TRRAP-mediated acetylation on Sp1 regulates adult neurogenesis. In Computational and structural biotechnology journal, 21, 472-484. doi:10.1016/j.csbj.2022.12.024. https://pubmed.ncbi.nlm.nih.gov/36618986/

3. Kang, Kyung-Taek, Shin, Min-Joo, Moon, Hye-Ji, Suh, Dong-Soo, Kim, Jae-Ho. 2023. TRRAP Enhances Cancer Stem Cell Characteristics by Regulating NANOG Protein Stability in Colon Cancer Cells. In International journal of molecular sciences, 24, . doi:10.3390/ijms24076260. https://pubmed.ncbi.nlm.nih.gov/37047234/

4. Suzuki, Taichi, Hirai, Yo, Uehara, Tomoko, Kosaki, Kenjiro, Kawahara, Atsuo. 2021. Involvement of the zebrafish trrap gene in craniofacial development. In Scientific reports, 11, 24166. doi:10.1038/s41598-021-03123-z. https://pubmed.ncbi.nlm.nih.gov/34934055/

5. Xia, Wenjun, Hu, Jiongjiong, Ma, Jing, Ma, Zhaoxin, Ma, Duan. 2019. Novel TRRAP mutation causes autosomal dominant non-syndromic hearing loss. In Clinical genetics, 96, 300-308. doi:10.1111/cge.13590. https://pubmed.ncbi.nlm.nih.gov/31231791/

6. Kang, Kyung Taek, Kwon, Yang Woo, Kim, Dae Kyoung, Suh, Dong-Soo, Kim, Jae Ho. . TRRAP stimulates the tumorigenic potential of ovarian cancer stem cells. In BMB reports, 51, 514-519. doi:. https://pubmed.ncbi.nlm.nih.gov/29936929/