INCENP(Inner Centromere Protein)是染色体乘客复合体(Chromosomal Passenger Complex, CPC)的核心成员之一,属于染色体乘客蛋白家族。该家族还包括Aurora B激酶、Survivin和Borealin,它们共同参与调控有丝分裂和减数分裂的关键过程,如染色体排列、纺锤体组装检查点、姐妹染色单体分离和胞质分裂。INCENP的主要功能是作为支架蛋白,稳定CPC的组装,并通过其C端区域激活Aurora B激酶的活性,从而确保细胞分裂的精确性。INCENP的作用位点主要集中在动粒(着丝粒)和纺锤体中区,随着细胞分裂进程动态迁移,最终定位于中体(midbody)调控胞质分裂。若INCENP发生突变(如截短或功能丧失突变),会导致Aurora B活性降低,引发染色体错误分离、非整倍体或胞质分裂失败,进而可能促进癌症发生。研究发现INCENP在多种肿瘤(如乳腺癌、结直肠癌)中过表达,与基因组不稳定性和不良预后相关。若INCENP表达降低,则会导致细胞分裂阻滞或异常退出有丝分裂,诱发细胞凋亡。此外,INCENP的异常表达还会影响其他CPC成员(如Survivin)的定位和功能,破坏微管-动粒连接的稳定性。该基因家族(染色体乘客蛋白家族)的共性在于动态的细胞周期依赖性定位变化、对Aurora B活性的调控作用以及维持基因组稳定性的核心功能。研究INCENP不仅有助于理解细胞分裂机制,也为开发靶向CPC的抗癌药物(如Aurora B抑制剂)提供了理论依据。
In mammalian cells, 2 broad groups of centromere-interacting proteins have been described: constitutively binding centromere proteins and 'passenger,' or transiently interacting, proteins (reviewed by Choo, 1997). The constitutive proteins include CENPA (centromere protein A; MIM 117139), CENPB (MIM 117140), CENPC1 (MIM 117141), and CENPD (MIM 117142). The term 'passenger proteins' encompasses a broad collection of proteins that localize to the centromere during specific stages of the cell cycle (Earnshaw and Mackay, 1994 [PubMed 8088460]). These include CENPE (MIM 117143); MCAK (MIM 604538); KID (MIM 603213); cytoplasmic dynein (e.g., MIM 600112); CliPs (e.g., MIM 179838); and CENPF/mitosin (MIM 600236). The inner centromere proteins (INCENPs) (Earnshaw and Cooke, 1991 [PubMed 1860899]), the initial members of the passenger protein group, display a broad localization along chromosomes in the early stages of mitosis but gradually become concentrated at centromeres as the cell cycle progresses into mid-metaphase. During telophase, the proteins are located within the midbody in the intercellular bridge, where they are discarded after cytokinesis (Cutts et al., 1999 [PubMed 10369859]).[supplied by OMIM, Mar 2008]
在哺乳动物细胞中,着丝粒相互作用蛋白2大类已经描述:组成性结合着丝粒蛋白质和“乘客”,或瞬时相互作用,蛋白质(由Choo的,1997中综述)。本构蛋白包括CENPA(着丝粒蛋白A; MIM 117139),CENPB(MIM 117140),CENPC1(MIM 117141)和CENPD(MIM 117142)。术语“乘客蛋白”包含,在细胞周期的特定阶段(恩绍和麦凯,1994 [搜索PubMed 8088460])定位于着丝粒蛋白质的广泛集合。这些措施包括CENPE(MIM 117143); MCAK(MIM 604538); KID(MIM 603213);胞质动力蛋白(例如,MIM 600112);夹(例如,MIM 179838);和CENPF /分裂激素(MIM 600236)。内着丝粒蛋白(INCENPs)(恩萧和库克,1991 [搜索PubMed 1860899]),乘客蛋白组的初始成员,在有丝分裂的早期阶段显示沿着染色体的广泛定位,但在着丝粒的细胞周期逐渐被浓缩进步入-中期中旬。期间末期,蛋白质位于中间体内的细胞间桥,在那里它们被胞质后丢弃(卡茨等人,1999年[搜索PubMed 10369859])。[由OMIM,2008年3月提供的]
INCENP基因(以及对应的蛋白质)的细胞分布位置:
INCENP基因的本体(GO)信息:
名称 |
---|
Cell Cycle |
Cell Cycle, Mitotic |
M Phase |
Mitotic Anaphase |
Mitotic Metaphase and Anaphase |
Mitotic Prometaphase |
Resolution of Sister Chromatid Cohesion |
RHO GTPase Effectors |
RHO GTPases Activate Formins |
Separation of Sister Chromatids |
Signal Transduction |
Signaling by Rho GTPases |
疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
melanoma | 0.12 | 1 | 0 | CTD_human |
Breast Carcinoma | 0.000271442 | 1 | 0 | BeFree |
Mammary Neoplasms | 0.000271442 | 1 | 1 | BeFree |
Stomach Carcinoma | 0.000271442 | 1 | 0 | BeFree |
Malignant neoplasm of breast | 0.000271442 | 1 | 0 | BeFree |
Malignant neoplasm of stomach | 0.000271442 | 1 | 0 | BeFree |
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