Cell death activator CIDE-A
Developmental stage
Expressed at 15 dpc in the interscapular region of the embryo, that could correspond to the developing brown adipose tissue. Expression continues in the interscapular region at 18 dpc and postnatally. In mammary glands, begins to be highly expressed at day 14.5 of pregnancy. Expression is maintained at high levels throughout lactation and declines during post-lactational involution.
Domain
The amphipathic helix mediates embedding into the lipid droplet phospholipid monolayer, promoting phosphatidic acid-binding, thereby facilitating triacylglycerol transfer.
The CIDE-N domain is involved in homodimerization which is crucial for its function in promoting lipid exchange and transfer.
Function
Lipid transferase that promotes unilocular lipid droplet formation by mediating lipid droplet fusion (PubMed:18509062, PubMed:22144693, PubMed:26609809, PubMed:36477540). Lipid droplet fusion promotes their enlargement, restricting lipolysis and favoring lipid storage (PubMed:18509062, PubMed:22144693, PubMed:26609809). Localizes on the lipid droplet surface, at focal contact sites between lipid droplets, and mediates atypical lipid droplet fusion by promoting directional net neutral lipid transfer from the smaller to larger lipid droplets (PubMed:18509062, PubMed:22144693, PubMed:26609809). The transfer direction may be driven by the internal pressure difference between the contacting lipid droplet pair and occurs at a lower rate than that promoted by CIDEC (PubMed:18509062, PubMed:22144693). May also act as a CEBPB coactivator in epithelial cells to control the expression of a subset of CEBPB downstream target genes, including ID2, IGF1, PRLR, SOCS1, SOCS3, XDH, but not casein (PubMed:22245780). By interacting with CEBPB, strengthens the association of CEBPB with the XDH promoter, increases histone acetylation and dissociates HDAC1 from the promoter (PubMed:22245780). When overexpressed, induces apoptosis; the physiological significance of its role in apoptosis is unclear (PubMed:9564035).
Sequence Similarities
Belongs to the CIDE family.
Tissue Specificity
Highly expressed in brown adipose tissue and, at lower levels, in white adipose tissue (at protein level) (PubMed:12910269, PubMed:18509062). Undetectable in undifferentiated preadipocytes (PubMed:12910269, PubMed:18509062). Expressed in mammary gland during pregnancy and lactation, in epithelial cells, but not in the surrounding adipose tissue (PubMed:22245780). Secreted into milk via milk fat globules (PubMed:22245780).
Cellular localization
- Lipid droplet
- Nucleus
- Enriched at lipid droplet contact sites (PubMed:18509062, PubMed:22144693). Using a GFP-tagged construct, has been shown to localize to mitochondria, where it could interact with UCP1 and hence inhibit UCP1 uncoupling activity (PubMed:12910269). These data could not be confirmed (PubMed:18509062, PubMed:22245780).
Alternative names
Lipid transferase CIDEA, Cell death activator CIDE-A, Cell death-inducing DFFA-like effector A, Cidea