The carboxy terminus of p53 mimics the polylysine effect of protein kinase CK2-catalyzed MDM2 phosphorylation
The carboxy terminus of p53 mimics the polylysine effect of protein kinase CK2-catalyzed MDM2 phosphorylation
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DOI：
10.1038/sj.onc.1201112
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发表时间：
1997-06-05
期刊：
影响因子：
8
通讯作者：
Issinger, OG
中科院分区：
文献类型：
--
作者：
Guerra, B;Gotz, C;Issinger, OG
癌基因产物MDM 2在体外可被蛋白激酶CK 2磷酸化，每摩尔MDM 2蛋白可掺入0.5-1 mol磷酸，（α-亚基）催化的磷酸盐掺入MDM 2蛋白质的量是全酶的两倍，与α-亚基催化的MDM 2磷酸化相比，多聚赖氨酸刺激CK 2全酶的MDM 2磷酸化三倍，当加入多聚赖氨酸时，α-亚基催化的MDM 2磷酸化降低约66%。全长p53，而且代表肿瘤抑制基因产物p53的C-末端片段的肽（氨基酸264-393，其还在氨基酸287-340处具有CK 2 β相互作用位点）在所有方面都模拟了多聚赖氨酸的作用，即通过CK 2全酶刺激磷酸盐掺入和在催化性CK 2 α-亚基存在下抑制。p53（264-393）的刺激平均接近两倍，α-亚基催化的MDM 2磷酸化的抑制约为40%。（WAF 1/CIP 1），已知是细胞周期蛋白依赖性蛋白激酶的有效抑制剂，也导致磷酸盐掺入MDM 2的显著减少，表明p21（WAF 1/CIP 1）并不完全抑制细胞周期激酶，此外，这些数据增加了对包括p21（WAF 1/CIP 1）、MDM 2蛋白、CK 2和p53在内的自动调节环的新认识。
The oncogene product MDM2 can be phosphorylated by protein kinase CK2 in vitro 0.5-1 mol of phosphate were incorporated per mol MDM2 protein, The catalytic subunit of protein kinase CK2 (alpha-subunit) catalyzed the incorporation of twice as much phosphate into the MDM2 protein as it was obtained with the holoenzyme, Polylysine stimulated MDM2 phosphorylation by CK2 holoenzyme threefold in contrast to the alpha-subunit-catalyzed MDM2 phosphorylation which was reduced by about 66% when polylysine was added, Full length p53, but also a peptide representing a C-terminal fragment of the tumor suppressor gene product p53 (amino acids 264-393 which also harbors the CK2 beta interaction site at amino acids 287-340) mimicked the polylysine effect in all respects, ie, stimulation of phosphate incorporation by CK2 holoenzyme and inhibition in the presence of the catalytic CK2 alpha-subunit. Stimulation by p53(264-393) was on the average close to twofold and inhibition in the case of the alpha-subunit-catalyzed MDM2 phosphorylation was about 40%, Phosphorylation of MDM2 by CK2 holoenzyme in the presence of the p21(WAF1/CIP1), known to be a potent inhibitor of cyclin-dependent protein kinases, also led to a significant reduction of phosphate incorporation into MDM2 indicating that p21(WAF1/CIP1) does not exclusively inhibit cell cycle kinases, Furthermore, these data add new insight into the autoregulatory loop which include p21(WAF1/CIP1), MDM2 protein, CK2 and p53.