Battle of the sexes: contrasting roles of testis-specific protein Y-encoded (TSPY) and TSPX in human oncogenesis.
Battle of the sexes: contrasting roles of testis-specific protein Y-encoded (TSPY) and TSPX in human oncogenesis.
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性别之战：人类肿瘤发生中睾丸特异性蛋白Y编码（TSPY）和TSPX的对比作用。
DOI：
10.4103/aja.aja_43_18
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发表时间：
2019-05
影响因子：
2.9
通讯作者：
Kido T
中科院分区：
文献类型：
--
作者：
Lau YC;Li Y;Kido T
Y染色体定位的睾丸特异性蛋白Y编码（TSPY）及其X染色体同源物TSPX起源于相同的祖先基因，但分别作为原癌基因和肿瘤抑制基因。TSPY具有专门的雄性特异性功能，而TSPX具有祖先基因的功能。TSPY和TSPX都具有保守的SET/NAP结构域，但在侧翼结构上是不同的。具体而言，TSPX含有C-末端酸性结构域，在TSPY中不存在。它们具有相反的性质，其中TSPY和TSPX分别加速和抑制细胞增殖，刺激和抑制细胞周期蛋白B-CDK 1磷酸化活性，对病毒HBx癌蛋白没有影响并促进蛋白体降解，并加剧和抑制雄激素受体（AR）和组成型活性AR变体，如AR-V7，基因反式激活。抑制结构域已被定位到TSPX中的羧基酸结构域，截短TSPX导致缩写的TSPX作为TSPY发挥积极作用。酸性结构域转座到TSPY的C末端会产生完整的TSPX抑制蛋白。因此，基因组突变/异常剪接事件可产生具有截短的酸性结构域和与TSPY相同的致癌特性的TSPX蛋白。此外，TSPY分别以配体依赖性和配体非依赖性方式被AR和AR-V7上调，表明Y定位的原癌基因和男性性激素/受体之间存在正反馈环，从而放大了人类癌症和疾病中各自的男性致癌作用。TSPX抵消了这种正反馈循环。因此，TSPY和TSPX是性染色体上的同源物，在人类致癌谱的两个极端发挥作用。
The Y-located testis-specific protein Y-encoded (TSPY) and its X-homologue TSPX originated from the same ancestral gene, but act as a proto-oncogene and a tumor suppressor gene, respectively. TSPY has specialized in male-specific functions, while TSPX has assumed the functions of the ancestral gene. Both TSPY and TSPX harbor a conserved SET/NAP domain, but are divergent at flanking structures. Specifically, TSPX contains a C-terminal acidic domain, absent in TSPY. They possess contrasting properties, in which TSPY and TSPX, respectively, accelerate and arrest cell proliferation, stimulate and inhibit cyclin B-CDK1 phosphorylation activities, have no effect and promote proteosomal degradation of the viral HBx oncoprotein, and exacerbate and repress androgen receptor (AR) and constitutively active AR variant, such as AR-V7, gene transactivation. The inhibitory domain has been mapped to the carboxyl acidic domain in TSPX, truncation of which results in an abbreviated TSPX exerting positive actions as TSPY. Transposition of the acidic domain to the C-terminus of TSPY results in an inhibitory protein as intact TSPX. Hence, genomic mutations/aberrant splicing events could generate TSPX proteins with truncated acidic domain and oncogenic properties as those for TSPY. Further, TSPY is upregulated by AR and AR-V7 in ligand-dependent and ligand-independent manners, respectively, suggesting the existence of a positive feedback loop between a Y-located proto-oncogene and male sex hormone/receptors, thereby amplifying the respective male oncogenic actions in human cancers and diseases. TSPX counteracts such positive feedback loop. Hence, TSPY and TSPX are homologues on the sex chromosomes that function at the two extremes of the human oncogenic spectrum.
DOI：
10.1111/bpa.12079
发表时间：
2014-01
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
--
作者：
Hervey-Jumper SL;Altshuler DB;Wang AC;He X;Maher CO;Robertson PL;Garton HJ;Fan X;Muraszko KM;Camelo-Piragua S
通讯作者：
Camelo-Piragua S