Bisio Alessandra, Ciribilli Yari, Fronza Gilberto, Inga Alberto, Monti Paola
Laboratory of Transcriptional Networks, Centre for Integrative Biology (CIBIO), University of Trento, Trento, Italy.
Hum Mutat. 2014 Jun;35(6):689-701. doi: 10.1002/humu.22514. Epub 2014 Mar 14.
Loss-of-function, partial-function, altered-function, dominant-negative, temperature sensitive, interfering, contact, structural, unfolded, misfolded, dimeric, monomeric, non-cooperative, unstable, supertrans, superstable, intragenic suppressor. TP53 mutants are many, more than 2,000 in fact, and they can be very diverse. Sporadic; germline; gain-of-function (GoF); oncogenic; rebel-angel; yin and yang; prion-like; metastasis-inducer; mediator of chemo-resistance; modifier of stemness. TP53 mutants can impact important cancer clinical variables, in multiple, often subtle ways, as revealed by cell-based assays as well as animal models. Here, we review studies investigating TP53 mutants for their effect on sequence-specific transactivation function, and especially recent findings on how TP53 mutants can exhibit GoF properties. We also review reports on TP53 mutants' impact on cancer cell transcriptomes and studies with Li-Fraumeni patients trying to classify and predict phenotypes in relation to experimentally determined transcription fingerprints. Finally, we provide an example of the complexity of correlating TP53 mutant functionality to clinical variables in sporadic cancer patients. Conflicting results and limitations of experimental approaches notwithstanding, the study of TP53 mutants has provided a rich body of knowledge, mostly available in the public domain and accessible through databases, which is beginning to impact cancer intervention strategies.
功能丧失、部分功能、功能改变、显性负性、温度敏感、干扰性、接触性、结构性、未折叠、错误折叠、二聚体、单体、非协同性、不稳定、超转录、超稳定、基因内抑制子。TP53突变体众多，实际上超过2000种，而且它们可能非常多样。散发性；种系性；功能获得（GoF）；致癌性；叛逆天使；阴阳；朊病毒样；转移诱导剂；化疗抗性介质；干性调节因子。如基于细胞的检测以及动物模型所揭示的，TP53突变体可以通过多种往往很微妙的方式影响重要的癌症临床变量。在此，我们综述了研究TP53突变体对序列特异性反式激活功能影响的研究，尤其是关于TP53突变体如何表现出功能获得特性的最新发现。我们还综述了关于TP53突变体对癌细胞转录组影响的报告以及对李-弗劳梅尼患者的研究，这些研究试图根据实验确定的转录指纹对表型进行分类和预测。最后，我们提供了一个将TP53突变体功能与散发性癌症患者临床变量相关联的复杂性的例子。尽管存在相互矛盾的结果和实验方法的局限性，但对TP53突变体的研究已经提供了丰富的知识体系，大多可在公共领域获取并可通过数据库访问，这正开始影响癌症干预策略。
