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Key Step In Programmed Cell Death Discovered 80

Investigators at St. Jude Children's Research Hospital have discovered a dance of proteins that protects certain cells from undergoing apoptosis, also known as programmed cell death. Understanding the fine points of apoptosis is important to researchers seeking ways to control this process. In a series of experiments, St. Jude researchers found that if any one of three molecules is missing, certain cells lose the ability to protect themselves from apoptosis. A report on this work appears in the advance online publication of Nature.
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Key Step In Programmed Cell Death Discovered

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  • by bytta ( 904762 ) on Saturday March 01, 2008 @12:30PM (#22610168)
    I for one welcome our dancing protein overlords.
  • so like when the new dancing proteins come out I will have the best internet handle.
  • Cancer applications? (Score:5, Interesting)

    by PinchDuck ( 199974 ) on Saturday March 01, 2008 @12:47PM (#22610256)
    I wonder if they could trigger apoptosis in cancer cells? That would be very cool
    • Re: (Score:3, Informative)

      by Rhabarber ( 1020311 )

      Everybody can kill cancer cells.

      The art is do do it selectively (to not kill everything else). No breakthrough here.
      • To be fair, many attempts have been made to selectively kill cancer cells. People used antibodies or toxins bound to molecules that bind to proteins typically expressed in a certain kind of cancer tissue. The problem is that even if you manage to kill 99.9% of your targets, there will always be some cancerous cells (often further mutated ones) being immune to your strategy. Those will proliferate and very soon you have a kind of cancer that cannot be treated any longer.
        • That's why I always thought the most successful treatments would be the ones that somehow exerted selective pressure to favor the weaker cells - those most vulnerable to a particular treatment, for example.

          Failing that, an "ensemble method" is probably the way to go, since cells that survive that would have to be immune to the intersection of every treatment you're throwing at them.

          Another idea that avoids the selectivity problem is to use things that cause cancerous cells to differentiate, rather than

      • by Tablizer ( 95088 )

        Everybody can kill cancer cells. The art is do do it selectively (to not kill everything else).

        Shit! I need to revise my medical contract before Dr. Brutus arrives for my treatment. I knew I left somethin' out. The contract looked too simple.
      • Re: (Score:3, Insightful)

        by radtea ( 464814 )
        No breakthrough here.

        Understanding the mechanisms of apoptosis is fundamental to understanding cancer. Cancer cells are typically "immortal". They do not undergo programmed cell death. This research, which demonstrates the role of these three proteins in protecting against apoptosis won't apply directly to cancer treatment, but will shed light on the gene networks responsible for regulating apoptosis, which will increase the odds of us learning how to turn it back on for cancer cells.

        This is part of the
    • Re: (Score:3, Insightful)

      by cpricejones ( 950353 )
      For normal cells to become cancer cells, they must become immortal. Immortalization generally involves alteration of normal cellular functions, such as the apoptosis machinery. So it's unlikely that the apoptosis pathway could be activated.
      • Immortal strikes me as the wrong choice of wording here, as these cells can still die quite easily. Aggressive would be a better fit, as the mutated cells have their suppression mechanisms deactivated, leading to proliferation of mutated cells which then spawn further mutations, and the cycle goes on until the cancer cells start invading surrounding tissue and/or metastasizing throughout the body.
        • Re: (Score:2, Informative)

          by cpricejones ( 950353 )
          Immortal is the word used when talking about cells that can persist indefinitely. One of the first types of mutations that cancer cells have is the mutation to activate hTERT, the telomerase gene.
    • Re: (Score:2, Insightful)

      by David Munch ( 939296 )
      The problem with cancercells is not killing them, we have loads of options on doing that. The problem is identifying them and killing them seperately and not affect surrounding tissue.
    • ....

      that would be the point. triggering it in cancer stem cells means you can excise a mass and the remaining cells die off.
    • by D.A. Zollinger ( 549301 ) on Saturday March 01, 2008 @03:10PM (#22610960) Homepage Journal

      Triggering apoptosis is the ultimate goal in cancer treatment. When a normal cell examines itself, and finds that it is genetically different, it will trigger apoptosis in order to sacrifice itself for the good of the being. Tumorigenic cells want to die, but for some reason the apoptosis mechanism never gets triggered, or is triggered and does not work. Therefore if researchers better understand what triggers apoptosis, then tumorigenic cells can be examined for those missing proteins. Perhaps if the apoptosis mechanism can be fixed, we will have a cure for the majority of cancer. There will still be a small number of tumorigenic cells which don't know they are different, thus have a perfectly working apoptosis mechanism which was never triggered.

      Lets try putting this in computer terms. Say when you copy a file by downloading it off the internet, the file itself wants to ensure you have an exact duplicate. Therefore the file performs its own CRC check once it is downloaded. If it fails the CRC check, it deletes itself and you have to download another copy. Now imagine this is a file sharing operation, thus your copy gets shared with many others who are downloading the file from you. If your copy became corrupt in the download process, yet didn't delete itself, a corrupt version of the file would be spread across the Internet (Pandemonium! Cats and dogs sleeping together! Chaos!). Thus wouldn't you want to fix the broken mechanism so that the corrupt file deleted itself, so that the process is started over? Unfortunately there is also a minuscule chance that a corrupt file will generate an identical CRC value thus never triggering the deletion.

      • Re: (Score:3, Funny)

        by Wordplay ( 54438 )
        Tumorigenic cells want to die ...and so begins the Goth Theory of cancer.
      • by KlomDark ( 6370 )
        Scary how much similarity there is between cancer cells and members of the Republican party.
    • Cancer the death of aging, killed or saved by immortality Part I Is an interesting perspective, which explores the idea that cancer is a failed immune response for repair. Part II includes the recently discovered by key to stopping wasting disease which improves the chances of not succumbing to cancer. Most people are not actually killed by cancer; the treatments kill them before it ever gets a chance, and the death certificates are actually false statements. Does anyone think it odd that the compounds use
  • Do nothing but snarky Bill Hicks-style smackdowns on the crappy pop acts ruining our culture and minds. This is "Falling Towards Apoptosis" with your host, Jollyreaper. Join me with the Christian Coalition -- they'll be smashing the CD's because they're immoral, I'll be smashing them because they suck.
  • by headkase ( 533448 ) on Saturday March 01, 2008 @01:04PM (#22610360)
    So can I be exposed to these three molecules in such a way that my immune system makes antibodies for them? Would be nice to be immunized against death.
    • by Slippy. ( 42536 )
      Sure. It's called cancer.

      Nothing says fun like knowing you're just one big tumor.
      • we cancer cells don't die, we multiply. Apoptosis makes us cry, but we will survive. /ends-bad-rap-'bout-cancer
    • Not quite (Score:4, Informative)

      by xplenumx ( 703804 ) on Saturday March 01, 2008 @01:44PM (#22610538)
      Three points:

      The proteins identified in the paper protect against apoptosis. If you were to inhibit them, your cells would be more susceptible to apoptosis, not more resistant (which they show using a knockout mouse). More importantly though, apoptosis is an essential process in both development and regulation (particularly the immune response). Indiscriminately inhibiting the apoptotic process would be detrimental to the organism as a whole (resulting in death, not the protection from).

      Let's say your body produced neutralizing antibodies to the three proteins (or better yet, you inject humanized antibodies that targeted the proteins), the antibodies would still have to penetrate the cell in order to see their target. You would be much better off making a tat-fusion protein of a dominant-negative form of the protein.

      Lastly, we've already identified several molecules that are important for apoptosis. One catagory of such proteins is call the Caspases [wikipedia.org].

    • by t_ban ( 875088 )

      So can I be exposed to these three molecules in such a way that my immune system makes antibodies for them? Would be nice to be immunized against death.

      "Millions wish for immortality who wouldn't know what to do with themselves on a slow Sunday afternoon"

      - A quote a read somewhere by someone I don't remember

  • by FudRucker ( 866063 ) on Saturday March 01, 2008 @01:08PM (#22610386)
    probably for only the rich & powerful, us unwashed masses wont get it, and if we do it will be available after i die of old age or some terrible disease...

    with over 6 billion people on earth just think if everyone got immortality and everyone making babies soon earth will be standing room only - yowsa!!!
    • Not dying of old age is only one part of it, plenty of war, hunger and disease to kill you still.
    • by Anonymous Coward on Saturday March 01, 2008 @01:56PM (#22610598)
      Solution is simple: free immortality, all you have to do is agree that you die if you ever have babies without permission. Not right away, but you start aging and eventually die as the treatment is reversed. Have a baby without permission, and grow old then die (your baby gets immortality treatment). That way when someone dies someone else gets an *authorized* baby, and the population remains stable. Maybe have a reversible sterilization (like a vasectomy) to prevent... accidents, while keeping baby-making ability in case of emergencies.

      Now, obviously that stinks of china's "one baby" policy... but if people aren't willing to stop having babies on their own, either someone else has to stop having babies for them, or more people have to die. There is just not enough room for all the babies people want to have, sometimes. And if people aren't dying of old age... well then they can't keep making babies.

      On a completely retarded sci-fi note... if we assume that we continue the trend of the west evolving into tall blond beautiful people, we stop aging about 20 and get quasi-immortality, and we advance science to the point where it looks like magic to most people and then integrate it into our biology and then our genetics... and then undergo an apocalypse so we forgot all this ever happened... Well then "we" get to be elves while people who didn't get (technology-so-advanced-it's-indistinguishable-from) magic, quasi-immortality, and a distinct look get to be regular humans. It could happen!
      • Well then "we" get to be elves while people who didn't get (technology-so-advanced-it's-indistinguishable-from) magic, quasi-immortality, and a distinct look get to be regular humans. It could happen!
        Perhaps it already has...
    • This is sort of a huge jump that you're making. Just because we can stop cells from dying doesn't mean that immortality is just over the horizon. Did you ever stop and think there is a reason cells die? Your cells are replaced every day with new copies as a natural process. I've read that, because of this process, no part of your body is more than 10 years old at any given time.
    • by Yvanhoe ( 564877 )
      The president of the Royal Society already pointed out that some very serious problems that we could encounter within ten or twenty years are considered only by SF writers. It is time that politicians realize and prepare for many likely scenarios.
      I for one believe that steps should be taken RIGHT NOW to decrease natality all over the world. The population lives longer, consumes more and more resources, it is a survival step to at least stabilize the world population.
    • by Tablizer ( 95088 )
      with over 6 billion people on earth just think if everyone got immortality and everyone making babies soon earth will be standing room only - yowsa!!!

      On the upside, Soylent Green is actually quite tasty, despite what the press says.
    • by Kenrod ( 188428 ) on Saturday March 01, 2008 @04:29PM (#22611352)

      Programmed cell death happens in cells that are ready to die because they have become damaged or non-functional in some way. If you stop this natural mechanism you won't get immortality, you get a body that dies much faster, probably within weeks.

      • "Programmed cell death happens in cells that are ready to die because they have become damaged or non-functional in some way. If you stop this natural mechanism you won't get immortality, you get a body that dies much faster, probably within weeks."

        I'm not quite sure how this was labelled "informative" since apoptosis is critical to development of every part of the body, if your cells didn't die, you would have a problem with 'fusion' and not develop your body parts properly (look at the toes), it's the sam
      • Either that, or zombies.
  • by Tablizer ( 95088 )
    When a cell's number is up, an enzyme stops by, checks to see that it only has 512 megs of RAM, and then installs Windows Vista on it. Biology is fascinating.

    -1 Offtopic
    -1 Troll
  • Actual article text (Score:5, Informative)

    by DebateG ( 1001165 ) on Saturday March 01, 2008 @01:46PM (#22610556)
    The actual abstract and article can be found on Nature's website and is entitled Hax1-mediated processing of HtrA2 by Parl allows survival of lymphocytes and neurons [nature.com]. Essentially what the researchers showed was that the gene Hax1 keeps cells alive when they aren't being stimulated with survival signals. This is interesting, for example, because cancer metastasis cells must survive in very foreign environments where they probably aren't receiving these factors. On the flip side, deficiencies in Hax1 results in blood cells dying early, causing a disease called severe congenital neutropenia.
  • "A research team elsewhere recently reported that Kostmann's syndrome, a potentially fatal inherited deficiency of granulocytes in children, caused by excessive apoptosis of granulocytes, results from a deficiency in one of the three proteins, called Hax1."

    So, basically, this disease occurs because one doesn't have "teh Hax(1)".

  • by sam_handelman ( 519767 ) <skh2003NO@SPAMcolumbia.edu> on Saturday March 01, 2008 @02:04PM (#22610660) Homepage Journal
    There are four general situations where apoptosis is medically interesting. This particular result increases our understanding of apoptsis generally, so is potentially relevant to all of them:

    a) Cancer. This is the big one. Your body has a natural defense against cancer - cells that would become cancerous undergo apoptosis and die. Only when this defense fails do you actually get cancer.

    b) Viral Infections. Viruses (and a few bacteria, but it's not the same thing) get inside the individual cells of your body and take them over to make viruses. Again, your body defends itself by inducing apoptosis in affected cells - the virus will typically contain genes to try and prevent this.

    c) Some degenerative diseases result from apoptosis being triggerred improperly in certain cells (Parkinsons' disease probably works this way.)

    d) Aptoptosis plays a major role in normal human development; if this goes wrong, this may cause certain development defects.
  • http://en.wikipedia.org/wiki/Bcl-2-associated_X_protein [wikipedia.org]

    Hax1, Pac1 and that other protein just help sequester this guy.
  • One step closer to a zombie invasion. Fire up the flame thrower, honey, it's gonna be a long night!
  • it looks like we're well on the way to discovering the Stileman Process.
  • All the inmates serving "Life-Sentences"....I know and understand this isnt an "immortality" prospect, in all reality, but just say it was, what WOULD we do wiht them at that point...Deny them an immortality prospect or not...I mean when the judgememnt of "life sentence" was issued the judge or jury prolly wasn't taking this into account... In light of that news, I'd have to say that the penal system would have to be reworked due to the fact that we wouldn't want to pay to keep inmates indeffinately in jai

To do two things at once is to do neither. -- Publilius Syrus