Interplay between HMGA and TP53 in cell cycle control along tumor progression
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Cellular and Molecular Life Sciences
REVIEW
Interplay between HMGA and TP53 in cell cycle control along tumor progression Nathalia Meireles Da Costa1 · Antonio Palumbo Jr2 · Marco De Martino3 · Alfredo Fusco3 · Luis Felipe Ribeiro Pinto1 · Luiz Eurico Nasciutti2 Received: 30 April 2020 / Revised: 5 August 2020 / Accepted: 3 September 2020 © Springer Nature Switzerland AG 2020
Abstract The high mobility group A (HMGA) proteins are found to be aberrantly expressed in several tumors. Studies (in vitro and in vivo) have shown that HMGA protein overexpression has a causative role in carcinogenesis process. HMGA proteins regulate cell cycle progression through distinct mechanisms which strongly influence its normal dynamics along malignant transformation. Tumor protein p53 (TP53) is the most frequently altered gene in cancer. The loss of its activity is recognized as the fall of a barrier that enables neoplastic transformation. Among the different functions, TP53 signaling pathway is tightly involved in control of cell cycle, with cell cycle arrest being the main biological outcome observed upon p53 activation, which prevents accumulation of damaged DNA, as well as genomic instability. Therefore, the interaction and opposing effects of HMGA and p53 proteins on regulation of cell cycle in normal and tumor cells are discussed in this review. HMGA proteins and p53 may reciprocally regulate the expression and/or activity of each other, leading to the counteraction of their regulation mechanisms at different stages of the cell cycle. The existence of a functional crosstalk between these proteins in the control of cell cycle could open the possibility of targeting HMGA and p53 in combination with other therapeutic strategies, particularly those that target cell cycle regulation, to improve the management and prognosis of cancer patients. Keywords HMGA · TP53 · Cell cycle · Cancer · Cell cycle-directed anti-cancer therapies
Introduction HMGA proteins The high mobility group A (HMGA) protein family is composed of HMGA1a, HMGA1b, and HMGA2. HMGA1a and HMGA1b proteins are encoded by the same gene, HMGA1, which is located at the chromosome band 6p21, whereas * Nathalia Meireles Da Costa [email protected] * Luiz Eurico Nasciutti [email protected]
HMGA2 is generated from HMGA2 gene located at the chromosome band 12q13-15 [1]. The HMGA proteins possess an N-terminus region harboring three basic domains known as AT-hooks, which are able to bind the AT-rich sequences in the minor groove of the DNA. They also possess a C-terminus region harboring the so-called acidic carboxyl-terminal domain, whose function still remains unclear. Indeed, the presence of many negatively charged amino acid residues 1
Programa de Carcinogênese Molecular, Instituto Nacional de Câncer-INCA, Rua André Cavalcanti, 37‑6th floor‑Centro, 20231‑050 Rio de Janeiro, RJ, Brazil
2
Laboratório de Interações Celulares, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro Prédio de Ciências da Saúde-Cidade Un
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