CDK1 phosphorylates NUP98

CDK1 activity promotes the nuclear pore complex (NPC) disassembly in mitosis (Muhlhausser and Kutay 2007). While NUP98 is probably not the only nucleoporin phosphorylated by CDK1 at mitotic entry, NUP98 is the best characterized CDK1 target among nuclear pore complex components. NUP98 threonine residues T529, T536, and T653, as well as serine residues S595 and S606 were found to be phosphorylated when NUP98 was isolated from mitotic HeLa cells (human cervical carcinoma cell line); these five sites match the CDK1 target site consensus and are phosphorylated by CDK1:CCNB in vitro (Laurell et al. 2011). The NUP98 splicing isoform NUP98-4 was used in the study by Laurell et al. 2011 and the indicated positions of phosphorylated amino acid residues refer to this isoform. An additional splicing isoform NUP98-3, the product of an alternative splicing site in exon10 of the NUP98 gene, which is 17 amino acids longer than NUP98-4, could also be a part of the NPC. CDK1-phosphorylated residues in NUP98-3 would be threonines T546, T553 and T670, and serines S612 and S623.

CDK1（周期蛋白依赖性激酶1）活性在有丝分裂过程中促进核孔复合体（NPC）的解聚（Muhlhausser and Kutay 2007）。尽管NUP98可能并非CDK1在有丝分裂起始时唯一磷酸化的核孔蛋白，但NUP98是核孔复合体成分中CDK1作用最为明确的靶标。当NUP98从有丝分裂的人HeLa细胞（一种人宫颈癌细胞系）中分离出来时，其苏氨酸残基T529、T536和T653，以及丝氨酸残基S595和S606被发现发生了磷酸化；这五个位点符合CDK1靶点共识，并在体外被CDK1:CCNB磷酸化（Laurell等，2011）。Laurell等人在2011年的研究中使用了NUP98剪接异构体NUP98-4，所指示的磷酸化氨基酸残基位置即指此异构体。另一种剪接异构体NUP98-3，是NUP98基因外显子10中一个选择性剪接位点产生的产物，比NUP98-4长17个氨基酸，也可能是NPC的组成部分。NUP98-3中CDK1磷酸化的残基为苏氨酸T546、T553和T670，以及丝氨酸S612和S623。