Introduction: Acetylation of histone and non-histone proteins is a post-translational modification mostly associated with activation of gene transcription. The first histone acetyltransferase (HAT) identified as modifying newly synthesized histone H4 at Lys5 and Lys12 was a type B HAT named HAT1. Although it was the first HAT to be discovered, it remains one of the most poorly studied enzymes in its class. In addition to its well-established role in the cytoplasm, recent findings have revealed new and intriguing aspects about the function of HAT1 in the nucleus. Purpose: Uncovering the non-canonical role of HAT1 first in DNA damage repair, then in chromatin assembly and chromatin maturation prompted in-depth investigations into the functional role of this protein in several biological processes. The involvement of HAT1 in regulating different pathways associated with a wide range of diseases, including cancer, and its contradictory role in carcinogenesis lead us to elucidate its role. Specifically, recent studies have shown that lower expression of HAT1 is associated with the pathogenesis of lung cancer 1, while in hepatocellular carcinoma, nasopharyngeal cancer, and pancreatic cancer 2–4 is highly expressed, acting as an oncogene, and linked to poor prognosis 4. Results and Conclusions: Immunoprecipitation experiment of overexpressed HAT1 combined with MS/MS analysis will be important to assess in which protein complexes HAT1 resides in breast cancer cell line. Moreover, genomics will be used for seeking possible molecular markers that can contribute at activating oncogenes or inactivating tumor suppressor genes. The main goal of this project is to understand HAT1 molecular mechanisms in cancer in order to develop novel strategy for cancer therapy. While efforts to identify molecules able to block its enzymatic activity are ongoing, the development of new compounds targeting one of its interactors could provide another entry point for HAT1 inhibition. REFERENCES
Characterization of Histone Acetyltransferase-1 in cancer cells
Angela Nebbioso;Lucia Altucci;Vincenzo Carafa
2020
Abstract
Introduction: Acetylation of histone and non-histone proteins is a post-translational modification mostly associated with activation of gene transcription. The first histone acetyltransferase (HAT) identified as modifying newly synthesized histone H4 at Lys5 and Lys12 was a type B HAT named HAT1. Although it was the first HAT to be discovered, it remains one of the most poorly studied enzymes in its class. In addition to its well-established role in the cytoplasm, recent findings have revealed new and intriguing aspects about the function of HAT1 in the nucleus. Purpose: Uncovering the non-canonical role of HAT1 first in DNA damage repair, then in chromatin assembly and chromatin maturation prompted in-depth investigations into the functional role of this protein in several biological processes. The involvement of HAT1 in regulating different pathways associated with a wide range of diseases, including cancer, and its contradictory role in carcinogenesis lead us to elucidate its role. Specifically, recent studies have shown that lower expression of HAT1 is associated with the pathogenesis of lung cancer 1, while in hepatocellular carcinoma, nasopharyngeal cancer, and pancreatic cancer 2–4 is highly expressed, acting as an oncogene, and linked to poor prognosis 4. Results and Conclusions: Immunoprecipitation experiment of overexpressed HAT1 combined with MS/MS analysis will be important to assess in which protein complexes HAT1 resides in breast cancer cell line. Moreover, genomics will be used for seeking possible molecular markers that can contribute at activating oncogenes or inactivating tumor suppressor genes. The main goal of this project is to understand HAT1 molecular mechanisms in cancer in order to develop novel strategy for cancer therapy. While efforts to identify molecules able to block its enzymatic activity are ongoing, the development of new compounds targeting one of its interactors could provide another entry point for HAT1 inhibition. REFERENCESI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
