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<\/a>Bcl-2 Family
\nThe Bcl-2 family regulates cell apoptosis through the effects of pro-apoptotic and anti-apoptotic members.\u00a0This family consists of more than 20 cytoplasmic proteins containing Bcl-2 homology (BH) domains, which are essential for the function of apoptosis.\u00a0Each member of the Bcl-2 family contains at least one BH motif to promote its function.\u00a0The members of the Bcl-2 family are divided into three functional categories, namely anti-apoptotic, pro-apoptotic multi-domain effector and only Bcl-2 homolog 3 (BH3) activator.
\nAmong them, the main family members are:<\/p>\n
Bcl-2<\/p>\n
Bcl-2<\/u><\/a>\u00a0is the initial member of the Bcl-2 family and plays a role in inhibiting cell apoptosis.\u00a0Bcl-2 is a ubiquitously expressed mitochondrial membrane protein, which can inhibit apoptotic cell death by isolating BAX and BAK.<\/p>\n PUMA NOXA<\/p>\n NOXA<\/u><\/a>\u00a0is the pro-apoptotic member of BH3-only in the Bcl-2 protein family.\u00a0Studies have found that NOXA is located in mitochondria and is the transcription target of p73 and p53.\u00a0NOXA replaces the pro-apoptotic proteins BAK and BIM from members of the anti-apoptotic protein Bcl-2 family, thereby promoting apoptosis during cell survival.\u00a0In addition, NOXA can also be upregulated independently of p53.<\/p>\n BAD<\/p>\n BAD<\/u><\/a>\u00a0is the only pro-apoptotic member of BH3 in the Bcl-2 protein family.\u00a0BAD has a pro-apoptotic effect, and its exact role in apoptotic signal transduction depends on the post-translational modification status of BAD.\u00a0Non-phosphorylated BAD forms heterodimers with two anti-apoptotic Bcl-2 protein family members, Bcl-xL and Bcl-2.\u00a0The combination of BAD and Bcl-xL promotes cell apoptosis by inhibiting the anti-apoptotic function of Bcl-xL.\u00a0After phosphorylation of serine, BAD cannot heterodimerize with Bcl-xL.\u00a0This combination retains BAD in the cytoplasm, allowing Bcl-xL to inhibit cell apoptosis.<\/p>\n BID<\/p>\n BID<\/u><\/a>\u00a0is a pro-apoptotic molecule that can form heterodimers with other members of the Bcl-2 family (including the agonist BAX or the antagonist Bcl-2).\u00a0BID contains a BH3 domain, which is required for its interaction with Bcl-2 family proteins and its pro-apoptotic activity.\u00a0BID is cleaved to produce a shorter active form called truncated BID (tBID).\u00a0tBID translocates to the mitochondria, leading to the activation of the intrinsic pathway.<\/p>\n BAX<\/p>\n BAX<\/u><\/a>, also known as Bcl-2-like protein 4 or Bcl-2-related X protein, is a member of the pro-apoptotic multi-domain effector family. After inducing apoptosis, BAX translocates to mitochondria and induces MOMP.<\/p>\n BAK<\/p>\n BAK<\/u><\/a>\u00a0is a member of the pro-apoptotic multi-domain effector family. Due to its similar structure to BAX, it is considered to have significant homology with BAX. The study found that Mcl-1 and Bcl-xL isolate BAK in non-apoptotic cells. After the onset of apoptosis, NOXA and BAD release BAK, which causes the outer mitochondrial membrane to permeate and release pro-apoptotic factors.<\/p>\n Extrinsic\u00a0Cell Death Pathway<\/p>\n After the death receptor binds to the ligand, the receptor oligomerizes and recruits adaptor proteins, such as serine\/threonine protein kinase 1 (RIPK1), RIPK3, and Fas-related proteins ( FADD), eventually formed as a death-inducing signaling complex (DISC).\u00a0As part of the DISC assembly, the former caspase 8 can be cleaved into its active form caspase-8 by oligomerization, which in turn cleaves and activates the effector caspase (caspase 3 and caspase 7). One of the early effects of this activation is the inhibition of phosphatidylserine (PS) flippase,\u00a0resulting in exposure of PS on the outer plasma membrane.<\/p>\n Early <\/b><\/strong>M<\/b><\/strong>arkers of <\/b><\/strong>Extrinsic Apoptotic Pathway<\/b><\/strong><\/p>\n Phospholipid Asymmetry<\/p>\n Phospholipid asymmetry is the controlled distribution of different lipid species in the lipid bilayer. One of the early apoptotic events is the rearrangement of lipids in the plasma membrane. This change causes PS to be exposed on the outer surface of the cell. This exposure depends on the inhibition of flippase and the signal from the phagocytic cell.<\/p>\n Annexin V<\/p>\n Fluorophore-conjugated annexin V is commonly used to assess changes in plasma membrane asymmetry. However, PS exposure may be short-lived, and this phenomenon is called “PS flip”. In the early detection of apoptosis, Annexin V and pSIVA can be used together with propidium iodide to distinguish dead cells from cells in the early stages of apoptosis.<\/p>\n Initiator Caspase<\/p>\n Caspase-8<\/u><\/a>\u00a0is the promoter caspase, a key signal molecule in the apoptosis mediated by CD95 and tumor necrosis factor receptor 1 (TNFR1). After activation, the cell death receptor Fas is connected to the adaptor molecule FADD through the corresponding death domain (DD). Then, FADD binds to procaspase 8 through the death effector domain (DED), and then undergoes oligomerization and autocatalytic activation. Activated caspase-8 cleaves and activates effector caspase and Bcl-2 family member BID. The activity of the starting protein caspase (caspase-8 and caspase-10) can be determined by Western blot or flow cytometry. The determination of caspase-8 activity by Western blotting depends on the detection of caspase-8 active fragments with a suitable caspase antibody.<\/p>\n Effector Caspases<\/p>\n Caspase-3<\/u><\/a>\u00a0and caspase-7<\/u><\/a>\u00a0are called “effector” caspases. The promoter caspase is automatically proteolyzed, and the effector caspase is cleaved by the promoter caspase. This hierarchical structure allows amplification of chain reactions. Effector caspases control many of the phenotypic changes observed during apoptosis, such as membrane blistering and DNA fragmentation.<\/p>\n","protected":false},"excerpt":{"rendered":" The early stages of apoptosis signal transduction involve a complex cascade of signal molecules.\u00a0Among them, early apoptosis signal transduction focuses on the activation of signal transduction molecules downstream of death receptors and\/or pro-apoptotic members of the B-cell lymphoma 2 (Bcl-2) pathway.\u00a0By detecting the early events of apoptosis, the pathway (external or internal) that induces apoptosis […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[55],"tags":[80],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/www.creative-diagnostics.com\/blog\/index.php\/wp-json\/wp\/v2\/posts\/1318"}],"collection":[{"href":"https:\/\/www.creative-diagnostics.com\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.creative-diagnostics.com\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.creative-diagnostics.com\/blog\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.creative-diagnostics.com\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=1318"}],"version-history":[{"count":2,"href":"https:\/\/www.creative-diagnostics.com\/blog\/index.php\/wp-json\/wp\/v2\/posts\/1318\/revisions"}],"predecessor-version":[{"id":1321,"href":"https:\/\/www.creative-diagnostics.com\/blog\/index.php\/wp-json\/wp\/v2\/posts\/1318\/revisions\/1321"}],"wp:attachment":[{"href":"https:\/\/www.creative-diagnostics.com\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=1318"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.creative-diagnostics.com\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=1318"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.creative-diagnostics.com\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=1318"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
\nPUMA, also known as Bcl-2 binding component 3 or JFY-1, is a member of the BH3-only protein family.\u00a0Studies have found that PUMA expression is regulated by p53 tumor suppressor protein.\u00a0When cells respond to stress and DNA damage, the up-regulated p53 binds to the PUMA promoter, resulting in PUMA transcription.\u00a0PUMA acts as a triggering factor for apoptosis through mitochondrial signal transduction and interaction with Bcl-xL, Bcl-2 and other anti-apoptotic proteins.<\/p>\n