Reading PAGE

Peer Evaluation activity

Collected by 1

Total impact ?

    Send a

    Gene has...

    Trusted 0
    Reviewed 0
    Emailed 0
    Shared/re-used 0
    Discussed 0
    Invited 0
    Collected 3

     

    This was brought to you by:

    block this user Gene Surov

    Independent researcher

    DonNU, Donetsk

    Depletion of the human Nα-terminal acetyltransferase A induces p53-dependent apoptosis and p53-independent growth inhibition

    Export to Mendeley

    The human protein N(α)-terminal acetyltransferase A complex (hNatA), composed of the catalytic hNaa10p (hArd1) and auxiliary hNaa15p (hNat1/NATH/Tubedown) subunits, was reported to be important for cell survival and growth of various types of cancer. However, little is known about the mechanisms mediating growth inhibition and apoptosis following loss of hNatA function. Here, we have screened 11 different thyroid cell lines for hNAA10 RNAi phenotypes and observed mostly growth inhibition, which was independent of TP53 functional status and developed by several different mechanisms involving (i) downregulation of cyclin D1, (ii) increase in p27/Kip1 and (iii) inactivation of Rb/E2F pathway. hNatA depletion in aggressive thyroid cancer cell lines (8305C, CAL-62 and FTC-133) with mutated TP53 increased sensitivity to drug-induced cytotoxicity, but in a cell type specific manner: 8305C (TRAIL), CAL-62 (daunorubicin) and FTC-133 (troglitazone). Cells harboring wild-type TP53 were also prone to apoptosis via the p53 pathway after hNatA downregulation. Importantly, in hNatA-depleted cells DNA-damage signaling was activated in the absence of exogenous DNA damage independent on TP53 status. Our findings indicate that several mechanisms of growth inhibition and apoptosis may be induced by hNatA knockdown and that hNatA knockdown could be exploited for use in combinatorial chemotherapy.

    Oh la laClose

    Your session has expired but don’t worry, your message
    has been saved.Please log in and we’ll bring you back
    to this page. You’ll just need to click “Send”.

    Your evaluation is of great value to our authors and readers. Many thanks for your time.

    Review Close

    Short review
    Select a comment
    Select a grade
    You and the author
    Anonymity My review is anonymous( Log in  or  Register )
    publish
    Close

    When you're done, click "publish"

    Only blue fields are mandatory.

    Relation to the author*
    Overall Comment*
    Anonymity* My review is anonymous( Log in  or  Register )
     

    Focus & Objectives*

    Have the objectives and the central topic been clearly introduced?

    Novelty & Originality*

    Do you consider this work to be an interesting contribution to knowledge?

    Arrangement, Transition and Logic

    Are the different sections of this work well arranged and distributed?

    Methodology & Results

    Is the author's methodology relevant to both the objectives and the results?

    Data Settings & Figures

    Were tables and figures appropriate and well conceived?

    References and bibliography

    Is this work well documented and has the bibliography been properly established?

    Writing

    Is this work well written, checked and edited?

    Write Your Review (you can paste text as well)
    Please be civil and constructive. Thank you.


    Grade (optional, N/A by default)

    N/A 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 10
    Close

    Your mailing list is currently empty.
    It will build up as you send messages
    and links to your peers.

     No one besides you has access to this list.
    Close
    Enter the e-mail addresses of your recipients in the box below.  Note: Peer Evaluation will NOT store these email addresses   log in
    Your recipients

    Your message:

    Your email : Your email address will not be stored or shared with others.

    Your message has been sent.

    Description

    Title : Depletion of the human Nα-terminal acetyltransferase A induces p53-dependent apoptosis and p53-independent growth inhibition
    Author(s) : Darina Gromyko, Thomas Arnesen, Anita Ryningen, Jan Erik Varhaug, Johan R. Lillehaug
    Abstract : The human protein N(α)-terminal acetyltransferase A complex (hNatA), composed of the catalytic hNaa10p (hArd1) and auxiliary hNaa15p (hNat1/NATH/Tubedown) subunits, was reported to be important for cell survival and growth of various types of cancer. However, little is known about the mechanisms mediating growth inhibition and apoptosis following loss of hNatA function. Here, we have screened 11 different thyroid cell lines for hNAA10 RNAi phenotypes and observed mostly growth inhibition, which was independent of TP53 functional status and developed by several different mechanisms involving (i) downregulation of cyclin D1, (ii) increase in p27/Kip1 and (iii) inactivation of Rb/E2F pathway. hNatA depletion in aggressive thyroid cancer cell lines (8305C, CAL-62 and FTC-133) with mutated TP53 increased sensitivity to drug-induced cytotoxicity, but in a cell type specific manner: 8305C (TRAIL), CAL-62 (daunorubicin) and FTC-133 (troglitazone). Cells harboring wild-type TP53 were also prone to apoptosis via the p53 pathway after hNatA downregulation. Importantly, in hNatA-depleted cells DNA-damage signaling was activated in the absence of exogenous DNA damage independent on TP53 status. Our findings indicate that several mechanisms of growth inhibition and apoptosis may be induced by hNatA knockdown and that hNatA knockdown could be exploited for use in combinatorial chemotherapy.
    Keywords : growth arrest, n terminal acetylation, naa10, nata

    Subject : unspecified
    Area : Other
    Language : English
    Year : 2010

    Affiliations DonNU, Donetsk
    Journal : International Journal of Cancer
    Volume : 127
    Issue : 12
    Pages : 2777 - 2789
    Url : http://doi.wiley.com/10.1002/ijc.25275
    Doi : 10.1002/ijc.25275

    Leave a comment

    This contribution has not been reviewed yet. review?

    You may receive the Trusted member label after :

    • Reviewing 10 uploads, whatever the media type.
    • Being trusted by 10 peers.
    • If you are blocked by 10 peers the "Trust label" will be suspended from your page. We encourage you to contact the administrator to contest the suspension.

    Does this seem fair to you? Please make your suggestions.

    Please select an affiliation to sign your evaluation:

    Cancel Evaluation Save

    Please select an affiliation:

    Cancel   Save

    Gene's Peer Evaluation activity

    Collected by 1

    Gene has...

    Trusted 0
    Reviewed 0
    Emailed 0
    Shared/re-used 0
    Discussed 0
    Invited 0
    Collected 3
    • Gene Surov, Independent researcher, DonNU, Donetsk.
    Invite this peer to...
    Title
    Start date (dd/mm/aaaa)
    Location
    URL
    Message
    send
    Close

    Full Text request

    Your request will be sent.

    Please enter your email address to be notified
    when this article becomes available

    Your email


     
    Your email address will not be shared or spammed.