HEC binds to the seventh regulatory subunit of the 26 S proteasome and modulates the proteolysis of mitotic cyclins.
A newly identified nuclear protein rich in leucine heptad repeats called HEC is important for mitosis. To elucidate its mechanism of action, the region containing leucine heptad repeats was used to identify cellular proteins that potentially interact with HEC. Complementary DNAs encoding several proteins including MSS1, p45, Nek2, and Smc1/Smc2, known to be important for G2/M progression, were identified. The interaction between HEC and MSS1, the seventh regulatory subunit of the 26 S proteasome, was further demonstrated by in vitro GST pull-down assays. HEC is not a part of the 26 S proteasome and interacts with MSS1 only when it is dissociated from the complex during M phase. Purified MSS1 specifically hydrolyzes ATP, an activity inhibited by HEC. In addition, HEC inhibits the proteolysis of mitotic cyclin B in vitro. Consistent with this biochemical activity, ectopic expression of HEC inhibits the degradation of mitotic cyclins after telophase, resulting eventually in cell death. These results show that HEC is a negative regulator of MSS1 and suggest that it may modulate M phase progression, in part, through the regulation of proteasome-mediated degradation of cell cycle regulatory proteins.
Chen
Y
Y
Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245-3207, USA.
Sharp
Z D
ZD
Lee
W H
WH
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006868:Hydrolysis; D008938:Mitosis; D009097:Multienzyme Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding
D016213:Cyclins; D004268:DNA-Binding Proteins; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; C075363:PSMC2 protein, human; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities