G1/S PHOSPHORYLATION OF THE RETINOBLASTOMA PROTEIN IS ASSOCIATED WITH AN ALTERED AFFINITY FOR THE NUCLEAR COMPARTMENT

被引:328
作者
MITTNACHT, S [1 ]
WEINBERG, RA [1 ]
机构
[1] MIT,DEPT BIOL,CAMBRIDGE,MA 02139
关键词
D O I
10.1016/0092-8674(91)90456-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hyperphosphorylation of the retinoblastoma protein (pRB) is assumed to be a regulatory event leading to the inactivation of its growth-repressing functions. We demonstrate a functional alteration linked to the phosphorylation status of the protein. The un- or under-phosphorylated species are tightly associated with the nuclear structure. The association is resistant to digestion with nucleases, and release requires elevated salt concentrations. In contrast, the hyperphosphorylated species are eluted under hypotonic buffer conditions. The conversion from low salt-resistant to low salt-extractable pRB occurs with transition through the G1/S boundary of the cell cycle and thus parallels the reported onset of pRB phosphorylation. The ability to form a tight nuclear association is impaired in several naturally occuring pRB mutants, all of which show alterations within the binding region for viral oncoproteins. We suggest that the tight nuclear interaction is essential for the growth-regulating functions of pRB and may be preempted by viral oncoproteins.
引用
收藏
页码:381 / 393
页数:13
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