NSD3(核受体结合SET结构域蛋白3)是NSD组蛋白甲基转移酶蛋白家族的成员。近年来,它已被确定为某些类型癌症的潜在癌基因。NSD3基因编码三种亚型,长版本(NSD3L),一个简短的版本(NSD3S)和WHISTLE亚型。重要的是,NSD3S同工型对应于全长蛋白的N末端区域,缺乏甲基转移酶结构域。NSD3的染色体位置经常在癌症类型中扩增,如乳房,肺,和结肠,在其他人中。最近,这种扩增与染色体增生事件相关,这可以解释在癌症中发现的不同的NSD3改变。含有NSD3的融合蛋白在白血病中也有报道(NSD3-NUP98),和NUT(睾丸核蛋白)中线癌(NSD3-NUT)。其作为癌基因的作用已被描述为通过其甲基转移酶活性调节不同的癌症途径,或者蛋白质的短同工型,通过蛋白质相互作用。具体来说,在这篇综述中,我们将重点讨论被表征为甲基转移酶依赖性的功能,以及与NSD3S同工型表达相关的那些。有证据表明,NSD3L和NSD3S同工型与癌症进展有关,建立NSD3作为治疗靶标。然而,需要进一步的功能研究来区分NSD3致癌活性是否依赖于或不依赖于蛋白质的催化结构域,以及每种同工型的贡献及其在癌症进展中的临床意义。
NSD3 (nuclear receptor-binding SET domain protein 3) is a member of the NSD histone methyltransferase family of proteins. In recent years, it has been identified as a potential oncogene in certain types of cancer. The NSD3 gene encodes three isoforms, the long version (NSD3L), a short version (NSD3S) and the WHISTLE isoforms. Importantly, the NSD3S isoform corresponds to the N-terminal region of the full-length protein, lacking the methyltransferase domain. The chromosomal location of NSD3 is frequently amplified across cancer types, such as breast, lung, and colon, among others. Recently, this amplification has been correlated to a chromothripsis event, that could explain the different NSD3 alterations found in cancer. The fusion proteins containing NSD3 have also been reported in leukemia (NSD3-NUP98), and in NUT (nuclear protein of the testis) midline carcinoma (NSD3-NUT). Its role as an oncogene has been described by modulating different cancer pathways through its methyltransferase activity, or the short isoform of the protein, through protein interactions. Specifically, in this review we will focus on the functions that have been characterized as methyltransferase dependent, and those that have been correlated with the expression of the NSD3S isoform. There is evidence that both the NSD3L and NSD3S isoforms are relevant for cancer progression, establishing NSD3 as a therapeutic target. However, further functional studies are needed to differentiate NSD3 oncogenic activity as dependent or independent of the catalytic domain of the protein, as well as the contribution of each isoform and its clinical significance in cancer progression.