Ubiquitin-dependent degradation of cyclin B is accelerated in polyploid megakaryocytes

被引:70
作者
Zhang, Y
Wang, ZY
Liu, DX
Pagano, M
Ravid, K
机构
[1] Boston Univ, Sch Med, Dept Biochem, Whitaker Cardiovasc Inst, Boston, MA 02118 USA
[2] NYU, Med Ctr, New York, NY 10016 USA
[3] NYU, Kaplan Canc Ctr, New York, NY 10016 USA
关键词
D O I
10.1074/jbc.273.3.1387
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
During the endomitotic cell cycle of megakaryocytic cell lines, the levels of cyclin B1 and the activity of cyclin B1-dependent Cdc2 kinase, although detectable, are reduced as compared with megakaryocytes undergoing a mitotic cell cycle, The levels of cyclin A, however, are comparable during both cell cycles, The expression of cyclin B1 mRNA is also equivalent in proliferating and polyploidizing cells, In the current study, we found that the rate of cyclin B1 protein degradation is enhanced in polyploidizing megakaryocytes, This finding has led us to further investigate whether the ubiquitin-proteosome pathway responsible for cyclin B degradation is accelerated in these cells, Our data indicate that polyploidizing megakaryocytic cell lines and primary bone marrow cells treated with the megakaryocyte proliferation-and ploidy-promoting factor, the c-Mpl ligand, display increased activities of the ubiquitin-proteosome pathway, which degrades cyclin B, as compared with proliferating megakaryocytic cell lines or diploid bone marrow cells, respectively. This degradation has all the hallmarks of a ubiquitin pathway, including the dependence on ATP, the appearance of high molecular weight conjugated forms of cyclin B, and inhibition of the proteolytic process by a mutated form of the ubiquitin-conjugating enzyme Ubc4., Our studies also indicate that the ability to degrade cyclin A is equivalent in both the mitotic and endomitotic cell cycles, The increased potential of polyploid megakaryocytes to degrade cyclin B may be part of the cellular programming that leads to aborted mitosis.
引用
收藏
页码:1387 / 1392
页数:6
相关论文
共 42 条
  • [31] The ubiquitin-mediated proteolytic pathway as a therapeutic area
    Rolfe, M
    Chiu, MI
    Pagano, M
    [J]. JOURNAL OF MOLECULAR MEDICINE-JMM, 1997, 75 (01): : 5 - 17
  • [32] Fission yeast pheromone blocks S-phase by inhibiting the G(1) cyclin B-p34(cdc2) kinase
    Stern, B
    Nurse, P
    [J]. EMBO JOURNAL, 1997, 16 (03) : 534 - 544
  • [33] DESTRUCTION OF XENOPUS CYCLIN-A AND CYCLIN-B2, BUT NOT CYCLIN-B1, REQUIRES BINDING TO P34(CDC2)
    STEWART, E
    KOBAYASHI, H
    HARRISON, D
    HUNT, T
    [J]. EMBO JOURNAL, 1994, 13 (03) : 584 - 594
  • [34] THE CYCLOSOME, A LARGE COMPLEX CONTAINING CYCLIN-SELECTIVE UBIQUITIN LIGASE ACTIVITY, TARGETS CYCLINS FOR DESTRUCTION AT THE END OF MITOSIS
    SUDAKIN, V
    GANOTH, D
    DAHAN, A
    HELLER, H
    HERSHKO, J
    LUCA, FC
    RUDERMAN, JV
    HERSHKO, A
    [J]. MOLECULAR BIOLOGY OF THE CELL, 1995, 6 (02) : 185 - 197
  • [35] Dominant-negative cyclin-selective ubiquitin carrier protein E2-C/UbcH10 blocks cells in metaphase
    Townsley, FM
    Aristarkhov, A
    Beck, S
    Hershko, A
    Ruderman, JV
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (06) : 2362 - 2367
  • [36] CDC27HS COLOCALIZES WITH CDC16HS TO THE CENTROSOME AND MITOTIC SPINDLE AND IS ESSENTIAL FOR THE METAPHASE TO ANAPHASE TRANSITION
    TUGENDREICH, S
    TOMKIEL, J
    EARNSHAW, W
    HIETER, P
    [J]. CELL, 1995, 81 (02) : 261 - 268
  • [37] UNCOUPLED CELL-CYCLE WITHOUT MITOSIS INDUCED BY A PROTEIN-KINASE INHIBITOR, K-252A
    USUI, T
    YOSHIDA, M
    ABE, K
    OSADA, H
    ISONO, K
    BEPPU, T
    [J]. JOURNAL OF CELL BIOLOGY, 1991, 115 (05) : 1275 - 1282
  • [38] CELL-CYCLE-REGULATED DEGRADATION OF XENOPUS CYCLIN B2 REQUIRES BINDING TO P34(CDC2)
    VANDERVELDEN, HMW
    LOHKA, MJ
    [J]. MOLECULAR BIOLOGY OF THE CELL, 1994, 5 (07) : 713 - 724
  • [39] Vitrat N, 1996, BLOOD, V88, P1135
  • [40] CYCLIN D3 IS ESSENTIAL FOR MEGAKARYOCYTOPOIESIS
    WANG, ZY
    ZHANG, Y
    KAMEN, D
    LEES, E
    RAVID, K
    [J]. BLOOD, 1995, 86 (10) : 3783 - 3788