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.

发现高迁移率 A 族 (HMGA) 蛋白在多种肿瘤中异常表达。研究（体外和体内）表明 HMGA 蛋白过度表达在致癌过程中具有致病作用。 HMGA 蛋白通过不同的机制调节细胞周期进程，这些机制强烈影响细胞恶性转化的正常动态。肿瘤蛋白 p53 ( TP53 ) 是癌症中最常改变的基因。其活性的丧失被认为是导致肿瘤转化的屏障的倒塌。在不同的功能中， TP53信号通路紧密参与细胞周期的控制，细胞周期停滞是p53激活后观察到的主要生物学结果，这可以防止受损DNA的积累以及基因组的不稳定。因此，本综述讨论了 HMGA 和 p53 蛋白对正常细胞和肿瘤细胞细胞周期调节的相互作用和相反作用。 HMGA蛋白和p53可能相互调节彼此的表达和/或活性，导致它们的调节机制在细胞周期的不同阶段产生抵消。这些蛋白质之间在细胞周期控制中存在的功能串扰可能开启了靶向 HMGA 和 p53 与其他治疗策略（特别是那些针对细胞周期调节的策略）相结合的可能性，以改善癌症患者的治疗和预后。