Nucleocytoplasmic shuttling of p130/RBL2: Novel regulatory mechanism

被引:55
作者
Chestukhin, A
Litovchick, L
Rudich, K
DeCaprio, JA
机构
[1] Dana Farber Canc Inst, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
关键词
D O I
10.1128/MCB.22.2.453-468.2002
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
The retinoblastoma-related pocket proteins pRb, p107, and p130 are implicated in the control of cell proliferation, differentiation, and transformation. The function of pocket proteins is in part mediated by their ability to inhibit specific E2F transcription factors. The transcriptional activity of E2Fs is controlled by alteration of their nucleocytoplasmic localization during the cell cycle. p130 was observed to shuttle between the nucleus and cytoplasm in a heterokaryon fusion assay, suggesting the presence of nuclear and cytoplasmic localization signals. Two independent nuclear localization signals (NLS) that could target reporter proteins to the nucleus in transient transfection and microinjection experiments were identified in the C terminus of p130. In addition to the C-terminal NLS, the intact pocket domain of p130 itself was sufficient for nuclear translocation. Moreover, an additional functional NLS was mapped within the unique Loop region of p130. An N-terminal domain that conferred cytoplasmic localization was identified. Removal of the entire N terminus did not affect the ability of p130 to interact with E2F and to induce growth arrest. A model suggesting that the activity of pRb family members can be regulated by intracellular trafficking of the proteins is proposed.
引用
收藏
页码:453 / 468
页数:16
相关论文
共 92 条
  • [61] A BINDING-SITE FOR TRANSCRIPTION FACTOR-E2F IS A TARGET FOR TRANSACTIVATION OF MURINE THYMIDINE KINASE BY POLYOMAVIRUS LARGE T-ANTIGEN AND PLAYS AN IMPORTANT ROLE IN GROWTH-REGULATION OF THE GENE
    OGRIS, E
    ROTHENEDER, H
    MUDRAK, I
    PICHLER, A
    WINTERSBERGER, E
    [J]. JOURNAL OF VIROLOGY, 1993, 67 (04) : 1765 - 1771
  • [62] Regulation of the cyclin E gene by transcription factor E2F1
    Ohtani, K
    DeGregori, J
    Nevins, JR
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (26) : 12146 - 12150
  • [63] SHUTTLING OF PRE-MESSENGER-RNA BINDING-PROTEINS BETWEEN NUCLEUS AND CYTOPLASM
    PINOLROMA, S
    DREYFUSS, G
    [J]. NATURE, 1992, 355 (6362) : 730 - 732
  • [64] Sambrook J, 1989, MOL CLONING LAB MANU, VII
  • [65] E2F-4 AND E2F-5, 2 MEMBERS OF THE E2F FAMILY, ARE EXPRESSED IN THE EARLY PHASES OF THE CELL-CYCLE
    SARDET, C
    VIDAL, M
    COBRINIK, D
    GENG, Y
    ONUFRYK, C
    CHEN, A
    WEINBERG, RA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (06) : 2403 - 2407
  • [66] THE CELL PROLIFERATION-ASSOCIATED ANTIGEN OF ANTIBODY KI-67 - A VERY LARGE, UBIQUITOUS NUCLEAR-PROTEIN WITH NUMEROUS REPEATED ELEMENTS, REPRESENTING A NEW KIND OF CELL CYCLE-MAINTAINING PROTEINS
    SCHLUTER, C
    DUCHROW, M
    WOHLENBERG, C
    BECKER, MHG
    KEY, G
    FLAD, HD
    GERDES, J
    [J]. JOURNAL OF CELL BIOLOGY, 1993, 123 (03) : 513 - 522
  • [67] CELL-CYCLE REGULATION OF THE CYCLIN-A GENE PROMOTER IS MEDIATED BY A VARIANT E2F SITE
    SCHULZE, A
    ZERFASS, K
    SPITKOVSKY, D
    MIDDENDORP, S
    BERGES, J
    HELIN, K
    JANSENDURR, P
    HENGLEIN, B
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (24) : 11264 - 11268
  • [68] SLANSKY JE, 1993, MOL CELL BIOL, V13, P7201
  • [69] A PROTEIN SYNTHESIS-DEPENDENT INCREASE IN E2F1 MESSENGER-RNA CORRELATES WITH GROWTH-REGULATION OF THE DIHYDROFOLATE-REDUCTASE PROMOTER
    SLANSKY, JE
    LI, Y
    KAELIN, WG
    FARNHAM, PJ
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (03) : 1610 - 1618
  • [70] Slansky JE, 1996, CURR TOP MICROBIOL, V208, P1