O'Connell M J, Norbury C, Nurse P
Cell Cycle Laboratory, Imperial Cancer Research Fund, London, UK.
EMBO J. 1994 Oct 17;13(20):4926-37. doi: 10.1002/j.1460-2075.1994.tb06820.x.
The NIMA protein kinase of Aspergillus nidulans is required for the G2/M transition of the cell cycle. Mutants lacking NIMA arrest without morphological characteristics of mitosis, but they do contain an activated p37nimX kinase (the Aspergillus homologue of p34cdc2). To gain a better understanding of NIMA function we have investigated the effects of expressing various NIMA constructs in Aspergillus, fission yeast and human cells. Our experiments have shown that the instability of the NIMA protein requires sequences in the non-catalytic C-terminus of the protein. Removal of this domain results in a stable protein that, once accumulated, promotes a lethal premature condensation of chromatin without any other aspects of mitosis. Similar effects were also observed in fission yeast and human cells accumulating Aspergillus NIMA. This phenotype is independent of cell cycle progression and does not require p34cdc2 kinase activity. As gain of NIMA function by accumulation results in premature chromatin condensation, and loss of NIMA function results in an inability to enter mitosis, we propose that NIMA functions in G2 to promote the condensation of chromatin normally associated with entry into mitosis.
构巢曲霉的NIMA蛋白激酶是细胞周期G2/M转换所必需的。缺乏NIMA的突变体停滞在没有有丝分裂形态特征的阶段，但它们确实含有活化的p37nimX激酶（p34cdc2的曲霉同源物）。为了更好地理解NIMA的功能，我们研究了在曲霉、裂殖酵母和人类细胞中表达各种NIMA构建体的影响。我们的实验表明，NIMA蛋白的不稳定性需要该蛋白非催化性C末端的序列。去除该结构域会产生一种稳定的蛋白，一旦积累，就会促进染色质的致命性过早凝聚，而没有任何有丝分裂的其他方面。在积累构巢曲霉NIMA的裂殖酵母和人类细胞中也观察到了类似的效应。这种表型与细胞周期进程无关，并且不需要p34cdc2激酶活性。由于通过积累获得NIMA功能会导致染色质过早凝聚，而丧失NIMA功能会导致无法进入有丝分裂，我们提出NIMA在G2期发挥作用，以促进通常与进入有丝分裂相关的染色质凝聚。
