Scholzen Thomas, Endl Elmar, Wohlenberg Claudia, van der Sar Sjaak, Cowell Ian G, Gerdes Johannes, Singh Prim B
Division of Molecular Immunology, Research Center Borstel, D-23845 Borstel, Germany.
J Pathol. 2002 Feb;196(2):135-44. doi: 10.1002/path.1016.
The expression of the nuclear protein Ki-67 (pKi-67) is strictly correlated with cell proliferation. Because of this, anti-Ki-67 antibodies can be used as operational markers to estimate the growth fraction of human neoplasia in situ. For a variety of tumours, the assessment of pKi-67 expression has repeatedly been proven to be of prognostic value for survival and tumour recurrence, but no cellular function has yet been ascribed to the Ki-67 protein. This study shows that a C-terminal domain of pKi-67 (Kon21) is able to bind to all three members of the mammalian heterochromatin protein 1 (HP1) family in vitro and in vivo. This interaction can be manipulated in living cells, as evidenced by ectopic expression of GFP-tagged HP1 proteins in HeLa cells, which results in a dramatic relocalization of endogenous pKi-67. Taken together, the data presented in this study suggest a role for pKi-67 in the control of higher-order chromatin structure.
核蛋白Ki-67(pKi-67)的表达与细胞增殖密切相关。因此,抗Ki-67抗体可作为评估人肿瘤原位生长分数的实用标志物。对于多种肿瘤,pKi-67表达的评估已反复被证明对生存和肿瘤复发具有预后价值,但Ki-67蛋白尚未被赋予任何细胞功能。本研究表明,pKi-67的C末端结构域(Kon21)在体外和体内均能与哺乳动物异染色质蛋白1(HP1)家族的所有三个成员结合。这种相互作用在活细胞中可以被调控,如在HeLa细胞中异位表达绿色荧光蛋白标记的HP1蛋白所证明的那样,这导致内源性pKi-67发生显著的重新定位。综上所述,本研究提供的数据表明pKi-67在控制高阶染色质结构中发挥作用。