Mimicking the BH3 domain to kill cancer cells.

Abstract:

:Cancer cells show deviant behavior that induces apoptotic signaling. To survive, cancer cells typically acquire changes enabling evasion of death signals. One way they do this is by increasing the expression of anti-apoptotic BCL-2 proteins. Anti-apoptotic BCL-2 family proteins antagonize death signaling by forming heterodimers with pro-death proteins. Heterodimer formation occurs through binding of the pro-apoptotic protein's BH3 domain into the hydrophobic cleft of anti-apoptotic proteins. The BH3 mimetics are small molecule antagonists of the anti-apoptotic BCL-2 members that function as competitive inhibitors by binding to the hydrophobic cleft. Under certain conditions, antagonism of anti-apoptotic BCL-2 family proteins can unleash pro-death molecules in cancer cells. Thus, the BH3 mimetics are a new class of cancer drugs that specifically target a mechanism of cancer cell survival to selectively kill cancer cells.

journal_name

Oncogene

journal_title

Oncogene

authors

Ni Chonghaile T,Letai A

doi

10.1038/onc.2009.52

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

S149-57

eissn

0950-9232

issn

1476-5594

pii

onc200952

journal_volume

27 Suppl 1

pub_type

杂志文章,评审

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