Table 2.

The biological activity of BCL-G demonstrated with distinct strength of evidence in diverse biological systems.

Major observations and findings	Experimental model	Activity of BCL-G	Strength of evidencea	Ref.
BCL-G is involved in vesicle trafficking and protein transport via interaction with the TRAPP complex	Bcl-g−/− mice; murine intestinal epithelial cells	Apoptosis-unrelatedb	High (in vivo and ex vivo; Bcl-g KO mice)	[28]
BCL-G prevents the progression of colitis-associated cancer via regulation of the mucin scaffolding network	Bcl-g−/− mice; murine small intestinal crypts	Apoptosis-unrelatedb	High (in vivo and ex vivo; Bcl-g KO mice)	[38]
BCL-G exerts an immunomodulatory activity via the regulation of secretion of chemokines: CCL5 and CCL20	Intestinal epithelial cells	Apoptosis-unrelatedb	High (BCL2L14 KO; induced overexpression of BCL-G; KD—siRNA)	[29]
BCL-G is involved in response to IFN-α2b by diminishing HIV replication	AIDS	Apoptosis-unrelated	Moderate (ex vivo; induced overexpression of BCL-G)	[40]
BCL-G contributes to DNA damage-induced apoptosis after G9a inhibition, and is involved in hepatocarcinogenesis	G9aΔHep mice; hepatocytes	Pro-apoptotic	Moderate (in vivo and ex vivo—G9aΔHep mice; induced overexpression of BCL-G; KD—shRNA)	[35]
BCL-GL promotes apoptosis in CD4+ T cells isolated from patients with systemic lupus erythematosus (SLE)	SLE	Pro-apoptotic	Moderate (ex vivo; induced overexpression of BCL-G; KD—shRNA)	[72]
BCL-G promotes apoptosis accompanying cerebral ischemia-reperfusion (I/R) injury	Neuroblastoma cells	Pro-apoptotic	Moderate (induced overexpression of BCL-G; KD—siRNA)	[42]
BCL-GL enhances basal apoptosis in COS7 cells	Monkey kidney fibroblast-like cells	Pro-apoptotic	Moderate (induced overexpression of BCL-G)	[50]
BCL-G contributes to ultraviolet-induced apoptosis	Breast/prostate cancer and embryonic kidney cells	Pro-apoptotic	Moderate (KD—siRNA)	[54, 83, 84]
BCL-G contributes to detrimental effects of glucose/oxygen deprivation, and nephrotoxicity of cisplatin	Kidney epithelial cells	Pro-apoptotic	Moderate (KD—shRNA)	[89]
BCL-G contributes to pterostilbene-induced apoptosis	Endometrial cancer	Pro-apoptotic	Moderate (KD—siRNA)	[41]
BCL-G downregulation accompanies acquisition of resistance to neratinib	Breast cancer	Pro-apoptoticc	Moderate (KD—shRNA)	[88]
BCL-G is upregulated by nano-particulate tetraiodothyroacetic acid	Breast cancer	Pro-apoptoticc	Low	[78]
BCL-G is upregulated after exposure to bilirubin or lithocholic acid	Osteosarcoma	Pro-apoptoticc	Low	[80]
BCL-G is upregulated during dexamethasone-induced apoptosis	Murine osteoblasts	Pro-apoptoticc	Low	[81]
BCL-G downregulation accompanies the healing of the skin	Thermal injury	Not yet determined	Low (ex vivo)	[43]
BCL-G is upregulated in bone marrow of patients treated with arsenic trioxide and ascorbic acid	Myelodysplasia	Not yet determined	Low (ex vivo)	[73]
BCL-G downregulation accompanies reduced activation of T cells	Murine T cells	Not yet determined	Low	[27]
BCL-G downregulation accompanies iodine-125 seed irradiation	Chondrosarcoma	Not yet determined	Low	[45]
BCL-G is upregulated under hyperbaric air conditions	Embryonic lung fibroblasts	Not yet determined	Low	[74]

Unless stated otherwise, the observations and findings were made in vitro and using human cells.

KD knockdown, KO knockout.

^a“Low” (observations), “moderate” (observations validated using a single method, or methods with high susceptibility to off-target effects [91]), “high” (solid results obtained using state-of-the-art genetic manipulations and numerous complementary methods [91]).

^bPro-apoptotic activity of BCL-G was questioned in experiments performed in parallel.

^cExpected pro-apoptotic activity of BCL-G requiring extensive experimental confirmation.