What specific mutations can cause the apoptosis mechanisms in a cell to malfunction? Are any such mutations 'reversible' , somehow or are they generally permanent? what kind of mutations can happen without disrupting the apoptosis mechanisms?

  • $\begingroup$ About which apoptosis pathway are you thinking, the intrinsic or the extrinsic? There are numerous proteins involved in controlling, promoting and preventing apoptosis, so this question is pretty broad at the moment. $\endgroup$
    – Chris
    Jul 14, 2015 at 19:46
  • $\begingroup$ I'm asking about any such pathways. I'm not asking about all the numerous intervening mechanisms which would be too broad. Is there a specific single mutation that can cause the apoptosis mechanisms to malfunction. Forgeting about any of the other contributing factors. What is one such mutation ( if a single mutation can do this)? $\endgroup$
    – 201044
    Jul 14, 2015 at 19:53
  • $\begingroup$ Wouldnt the mutations be in whatever genes code for whatever proteins responsible for apoptosis are? $\endgroup$
    – Ro Siv
    Jul 14, 2015 at 20:17
  • $\begingroup$ That's interesting where such mutations would be; but I'm asking for the designation of one such mutation. $\endgroup$
    – 201044
    Jul 14, 2015 at 20:20
  • 2
    $\begingroup$ Read the full text of Hallmarks of Cancer: The Next Generation down in the section titled "Resisting Cell Death." I'd read the full article, however. $\endgroup$
    – CKM
    Jul 14, 2015 at 20:43

1 Answer 1


There are lots and lots of specific single mutations that cause problems with apoptosis.

Some of the most common are in P53, PTEN, MYC, APC, and KRAS. If you want a specific amino acid change, KRAS G12D is particularly potent. It works by disabling a regulatory domain and causing KRAS to be constitutively active.

These aren't "reversible" in a strict sense (except, I guess, for the struck-by-lightning-while-holding-a-winning-lottery-ticket level improbability of a second replication error in the same place back to the original base) but in many cases the cells will upregulate compensatory pathways or activate senescence pathways instead, rather than instantaneously becoming full-blown malignant.

As for mutations that don't cause disruptions to apoptosis,there are almost an infinite number, in that silent mutations or mutations to genes that aren't involved in apoptosis would count.

If you mean what kind of non-silent mutations can happen to genes that are important to apoptosis without causing problems, there are still a lot: swapping similar amino acids in non-active parts of proteins are unlikely to have huge effects.

  • $\begingroup$ If a cell develops KRAS G12D , a potent mutation why is this cell itself hard 'to detect' by the immune system? A lot of these mutations that harm or shut-off the apoptosis mechanisms in various cells are not 'seen' by the immune system; are these mutation changes 'masked' by some biological processes? $\endgroup$
    – 201044
    Jul 16, 2015 at 13:20
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    $\begingroup$ Tumor immunosurveillance is a whole new topic worth its own question, but there are two basic reasons: (1) Mutated KRAS is not immunologically very different from wild-type KRAS-- it just doesn't change the overall surface shape of the protein that much, and (2) even when the immune system does recognize mutated cell products, the tumor cells react by upregulating anti-inflammatory pathways, such as recruiting regulatory T cells. $\endgroup$ Jul 16, 2015 at 13:52
  • $\begingroup$ So tumor cells can use regulatory Tcells? It sounds like a tumor cell can hijack various parts of the immune system. Maybe since tumor cells are 'non-foreign' 'formerly regular' cells they have access to and can use any part of the immune system. $\endgroup$
    – 201044
    Jul 16, 2015 at 14:02
  • $\begingroup$ That's part of it. They also downregulate their MHC complexes and secrete their own inhibitory cytokines. It's a big and complicated problem that's had a lot of research done on it. Here's a review: ncbi.nlm.nih.gov/pmc/articles/PMC1857231 $\endgroup$ Jul 16, 2015 at 14:54
  • $\begingroup$ Even though it's a complicated problem is there a way to stop or supress a tumors ability to use parts of the immune system , like T cells. $\endgroup$
    – 201044
    Jul 20, 2015 at 14:02

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