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bcl-xL
Function:
- inhibits apoptosis through a bax-independent mechanism
- associates with caspase 9 & APAF-1, inhibiting maturation of caspase 9 mediated by APAF-1 [4]
- deamidation of bcl-xL with increased intracellular pH resulting from phosphorylation of NHE1 after DNA damage abrogates antiapoptic activity of bcl-xL [5]
- overexpression leads to increased numbers of mature thymocytes
Pathology:
- BCR-ABL fusion gene may inhibit Bcl-xL deamidation in patients with CML [5]
- JAK2 mutation may inhibit Bcl-xL deamidation in patients with polycythemia vera &/or myelofibrosis [5]
Pharmacology:
- UBX1325 binds to Bcl-xL & selectively induces apoptosis in senescent cells [6]
- a single dose of UBX1325 improved visula acuity in patients with diabetic macular edema or neovascular age-related macular degeneration [6]
Interactions
molecular events
General
anti apoptotic protein
Bcl-2-like protein 1; Bcl2-L-1; apoptosis regulator Bcl-X (BCL2L1, BCL2L, BCLX)
Properties
SIZE: entity length = 233 aa
COMPARTMENT: mitochondria
cytoplasm
nuclear membrane
MOTIF: BH4 domain
NAME: BH4 domain
SITE: S4-W24
BH3 domain
NAME: BH3 domain
SITE: V86-R100
BH1 domain
NAME: BH1 domain
SITE: E129-G148
BH2 domain
NAME: BH2 domain
SITE: P180-Y195
transmembrane domain {F210-L226}
References
- Boise LH et al
bcl-x, a bcl-2-related gene that functions as a dominant
regulator of apoptotic cell death.
Cell. 1993 Aug 27;74(4):597-608.
PMID: 8358789
- Cheng EH, Levine B, Boise LH, Thompson CB, Hardwick JM.
Bax-independent inhibition of apoptosis by Bcl-XL.
Nature. 1996 Feb 8;379(6565):554-6.
PMID: 8596636
- Yang XF, Weber GF, Cantor H.
A novel Bcl-x isoform connected to the T cell receptor
regulates apoptosis in T cells.
Immunity. 1997 Nov;7(5):629-39.
PMID: 9390687
- Hu Y et al
Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent
caspase-9 activation.
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4386-91.
PMID: 9539746
- Zhao R et al.
Inhibition of the Bcl-xL deamidation pathway in
myeloproliferative disorders.
N Engl J Med 2008 Dec 25; 359:2778.
PMID: 19109573
- Bankhead C
'Senolytic' Therapy Shows Promise in Neovascular Eye Disease.
Clearing out dying cells, approach has implications far beyond ophthalmology.
MedPage Today July 14, 2022
https://www.medpagetoday.com/meetingcoverage/asrs/99734
Component-of
molecular complex