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    Cell Cycle Regulation

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    Ahmed Fazly
    The core components of the cell-cycle control system are governed by numerous additional regulators, which ensure that cyclin-dependent kinase (Cdk) and anaphase-promoting complex (APC) activities are robustly and rapidly activated in the correct order and at the appropriate cell-cycle stage. Progression through the cell cycle depends in part on transcriptional regulators, including the particularly well-understood regulators of G1/S gene expression at the beginning of the cycle. Although the details vary among different species, the general scheme of eukaryotic cell-cycle control can be summarized as follows.

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    Cell Cycle Regulation

    Uploaded by

    Ahmed Fazly
    147 views2 pages
    The core components of the cell-cycle control system are governed by numerous additional regulators, which ensure that cyclin-dependent kinase (Cdk) and anaphase-promoting complex (APC) activities are robustly and rapidly activated in the correct order and at the appropriate cell-cycle stage. Progression through the cell cycle depends in part on transcriptional regulators, including the particularly well-understood regulators of G1/S gene expression at the beginning of the cycle. Although the details vary among different species, the general scheme of eukaryotic cell-cycle control can be summarized as follows.

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    Cell cycle

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    The core components of the cell-cycle control system are governed by numerous additional regulators, which ensure that cyclin-dependent kinase (Cdk) and anaphase-promoting complex (APC) activities are robustly and rapidly activated in the correct order and at the appropriate cell-cycle stage. Progression through the cell cycle depends in part on transcriptional regulators, including the particularly well-understood regulators of G1/S gene expression at the beginning of the cycle. Although the details vary among different species, the general scheme of eukaryotic cell-cycle control can be summarized as follows.

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    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
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    147 views2 pages

    Cell Cycle Regulation

    Uploaded by

    Ahmed Fazly
    The core components of the cell-cycle control system are governed by numerous additional regulators, which ensure that cyclin-dependent kinase (Cdk) and anaphase-promoting complex (APC) activities are robustly and rapidly activated in the correct order and at the appropriate cell-cycle stage. Progression through the cell cycle depends in part on transcriptional regulators, including the particularly well-understood regulators of G1/S gene expression at the beginning of the cycle. Although the details vary among different species, the general scheme of eukaryotic cell-cycle control can be summarized as follows.

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    of 2

    SnapShot: Cell-Cycle Regulators II

    David O. Morgan
    University of California, San Francisco, CA 94143, USA

    function

    S. cerevisiae
    (Budding Yeast)

    S. pombe
    (fission Yeast)

    D. melanogaster
    (fruit fly)

    X. laevis
    (clawed Toad)

    H. sapiens
    (Human)

    Cdk-inhibitory
    kinases

    Phosphorylate
    Cdk in active site,
    blocking activity

    swe1

    Wee1, Mik1

    Dwee1, Dmyt1

    Wee1, Myt1

    Wee1, Myt1

    Cdk-activating
    phosphatases

    Dephosphorylate
    inhibitory
    phosphorylation of
    Cdk subunit

    Mih1

    cdc25

    string, Twine

    cdc25A, B, c

    cdc25A, B, c

    Cdk inhibitor
    proteins (CKIs)
    (selected)

    Sic1 class:
    inhibits S and M
    phase Cdks

    sic1

    Rum1

    Roughex (Rux)

    Xic1 (Kix1)

    p21 (Cip1, Waf1),


    p27 (Kip1), p57
    (Kip2)

    Dacapo (Dap)

    Cip/Kip class:
    inhibits G1, S, M
    phase Cdks and
    activates G1 Cdks

    p15Ink4b, p16Ink4a,
    p18Ink4c, p19Ink4d

    INK4 class:
    inhibits G1 Cdks
    APC inhibitors
    (selected)

    Bind activating
    subunit, often as
    pseudosubstrates

    Acm1 binds Cdh1

    SCF (Skp1Cullin-F box)


    ubiquitin ligase
    F-box subunits
    (selected)

    Recruit indicated
    substrates to
    SCF ligase for
    ubiquitination

    cdc4 recruits
    Sic1, Far1, Cdc6

    Mes1 binds
    Cdc20 in meiosis

    Rca1 binds Cdh1

    emi1 binds
    Cdc20 and Cdh1
    fbw7 (Cdc4,
    Ago) recruits
    cyclin E
    -TrcP1 recruits
    Cdc25A, Wee1,
    Emi1

    Grr1 recruits
    Cln1, 2
    G1/S gene
    control

    Xerp1 (Emi2)
    binds Cdc20 in
    meiosis

    skp2 recruits
    E2F-1, p27

    Transcription factors: Sequence-specific DNA-binding proteins at G1/S gene promoters


    sBf (Swi6 +
    Swi4): activator

    de2f1: activator

    e2f-1, 2, 3:
    activators

    MBf (Swi6 +
    Mbp1): regulator

    de2f2: repressor

    e2f4, 5:
    repressors

    Cdk-dependent inhibitors: Inhibit activators or assist repressors; inhibited by G1-Cdk


    Whi5

    974 Cell 135, November 28, 2008 2008 Elsevier Inc.

    dRBf1, dRBf2

    DOI 10.1016/j.cell.2008.10.040

    pRB, p107, p130

    See online version for legend and references.

    SnapShot: Cell-Cycle Regulators II


    David O. Morgan
    University of California, San Francisco, CA 94143, USA
    The core components of the cell-cycle control system are governed by numerous additional regulators, which ensure that cyclin-dependent kinase (Cdk) and anaphasepromoting complex (APC) activities are robustly and rapidly activated in the correct order and at the appropriate cell-cycle stage. Cyclin-Cdk activities are controlled by
    phosphorylation at inhibitory sites on the Cdk subunit, association with Cdk-inhibitory proteins (CKIs), transcriptional control of cyclins and other regulators, and the ubiquitin-dependent proteolysis of cyclins and CKIs. APC activity is fine-tuned by inhibitory proteins that restrain its function outside mitosis.
    A multisubunit ubiquitin ligase called SCF contributes to early cell-cycle control by triggering the ubiquitination and destruction of some CKIs and G1/S cyclins. The SCF
    core (containing three subunits, not listed here) interacts with numerous F-box proteins that recruit specific substrates for ubiquitination. Typically, SCF targets must be
    phosphorylated by Cdks or other kinases to allow their recognition by F-box subunits of SCF.
    Progression through the cell cycle depends in part on transcriptional regulators, including the particularly well-understood regulators of G1/S gene expression at the beginning of the cycle. Prior to cell-cycle entry, these regulators interact with inhibitor proteins, blocking the activation of G1/S gene expression and, in some cases, actively
    repressing it. G1-Cdks phosphorylate and thereby inactivate these inhibitors, unleashing G1/S gene expression.
    Although the details vary among different species, the general scheme of eukaryotic cell-cycle control can be summarized as follows. In response to the appropriate extracellular signals or cell size, G1-Cdks trigger G1/S gene expression, leading to expression of G1/S and S cyclins and other components required for S phase events. G1/S-Cdk
    activation helps promote S-Cdk activation, at least in some cases, by phosphorylating CKIs and thereby targeting them to SCF for ubiquitination. G1/S- and S-Cdks then
    collaborate to initiate chromosome duplication and duplication of the spindle poles. M cyclins rise during S phase or thereafter, but M-Cdk complexes are initially restrained in
    many species by inhibitory phosphorylation by Wee1-related inhibitory kinases. Dephosphorylation by Cdc25-related phosphatases then triggers M-Cdk activation, resulting
    in mitotic spindle assembly and other preparations for chromosome segregation. When the chromosomes are aligned on the spindle, activation of APCCdc20 initiates sisterchromatid separation and Cdk inactivation, leading to dephosphorylation of Cdk substrates and the completion of mitosis and cytokinesis. Declining Cdk activity results in
    the activation of APCCdh1, which continues to suppress cyclin levels until it is inactivated by Cdks at the beginning of the next cell cycle.
    Multiple additional regulators, not listed here, collaborate with Cdks and the APC to govern cell-cycle events. In mitosis, for example, the protein kinases Plk1, Aurora A, and
    Aurora B contribute in multiple ways to the control of mitotic spindle and chromosome function. Plk1 stimulates mitotic progression in part by promoting Cdc25 activation
    and inhibiting the APC inhibitor Emi1. Mitotic progression also depends on a regulatory system called the spindle assembly checkpoint, which suppresses APCCdc20 activity
    until all sister chromatid pairs are correctly attached to both spindle poles. APCCdc20 activity is directly inhibited by checkpoint components, notably Mad2 and Mad3, which
    bind and inhibit Cdc20 before metaphase but are released from Cdc20 when chromosome alignment occurs.

    Abbreviations
    Cdk, cyclin-dependent kinase; CKI, Cdk-inhibitory protein; APC, anaphase-promoting complex or cyclosome; SCF, Skp1-Cullin-F box complex.
    References
    Attwooll, C., Lazzerini Denchi, E., and Helin, K. (2004). The E2F family: specific functions and overlapping interests. EMBO J. 23, 47094716.
    Cardozo, T., and Pagano, M. (2004). The SCF ubiquitin ligase: insights into a molecular machine. Nat. Rev. Mol. Cell Biol. 5, 739751.
    Morgan, D.O. (2007). The Cell Cycle: Principles of Control (London: New Science Press).
    Peters, J.M. (2006). The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat. Rev. Mol. Cell Biol. 7, 644656.
    Wittenberg, C., and Reed, S.I. (2005). Cell cycle-dependent transcription in yeast: promoters, transcription factors, and transcriptomes. Oncogene 24, 27462755.

    974.e1 Cell 135, November 28, 2008 2008 Elsevier Inc. DOI 10.1016/j.cell.2008.10.040

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