Table 3.

NF-κB induced genes dependent on both GSK3β and PKR.

Gene/protein	Stimulation	Method used	aFunction	Ref. #
A1/Bfl-1	TNFα stimulation in PKR+/+ and −/− MEFs	Western blot	A1 is an anti-apoptotic BCL-2 family protein that binds BAX thus inhibiting cytochrome c release and caspase 3 activation.	[49,135]
	TNFα stimulation in GSK3β+/+ and −/− MEFs	Western blot
BCL-XL	TNFα stimulation in PKR+/+ and −/− MEFs	Western blot	BCL-XL is the major hematopoetic anti-apoptotic BCL-2 family member. BCL-XL is best known for its ability to bind BAX blocking the homodimerization of BAX and the initiation of the caspase-9 mediated apoptotic pathway.	[49,135,136]
	TNFα stimulation in GSK3β+/+ and −/− MEFs; treatment of pancreatic cancer cell lines with a pharmacological inhibitor of GSK3β siRNA	Western blot
Cyclin D1	TNFα stimulation in PKR+/+ and −/− MEFs	Western blot	Controls entry into S-phase of the cell cycle. Cyclin D1 is a target of both MYC and NF-κB. Cyclin D1 in association with CDK4/6 phosphorylate the retinoblastoma protein (Rb) resulting in the release of E2F and the transcription of cell cycle promoting genes. Overexpression of cyclin D1 is associated with enhanced cell proliferation.	[49,135,136]
	TNFα stimulation in GSK3β+/+ and −/− MEFs; treatment of pancreatic cancer cell lines with a pharmacological inhibitor of GSK3β siRNA	Western blot
FLIP	TNFα stimulation in PKR+/+ and −/− MEFs	Western blot	FLICE inhibitor protein associates with caspase 8, FADD, caspase 3, TRAF1 and TRAF2. Expression of full-length FLIP (FLIPL) or the C-ter domain is pro-apoptotic while a splice variant lacking the C-ter (FLIPS) is anti-apoptotic in response to death receptor mediated apoptosis. Loss of FLIP is embryonic lethal in mice due to lack of proper heart development. FLIP−/− embryonic fibroblasts were hypersensitive to TNFα- and FAS-mediated apoptosis.	[49,135]
	TNFα stimulation in GSK3β+/+ and −/− MEFs	Western blot
c-IAP-1	Tet-inducible PKR/TNFα stimulation in PKR+/+ and −/− MEFs	cDNA array/Western blot	Inhibitor of apoptosis protein-1, -2 and XIAP block the induction of apoptosis by associating with cytosolic regions of death domain containing receptors to block the induction of associated caspases such as caspase 8.	[49,57,135]
	TNFα stimulation in GSK3β+/+ and −/− MEFs	Western blot
c-IAP-2	Tet-inducible PKR/TNFα stimulation in PKR+/+ and −/− MEFs	cDNA array/Western blot	Inhibitor of apoptosis protein-1, -2 and XIAP block the induction of apoptosis by associating with cytosolic regions of death domain containing receptors to block the induction of associated caspases such as caspase 8.	[57,135]
	TNFα stimulation in GSK3β+/+ and −/− MEFs	Western blot
MMP-9	TNFα stimulation in PKR+/+ and −/− MEFs	Western blot	Matrix metalloproteinase 9 is a member of a family of extracellular proteases that degrade Type IV and V collagens. MMP9 has been shown to be involved in vascularization, tissue remodeling, angiogenesis, and migration. MMP9 was shown to have a significant role in mobilization of hematopoeitic stem cells from the bone marrow induced by IL8.	[49,135]
	TNFα stimulation in GSK3β+/+ and −/− MEFs	Western blot
XIAP	TNFα stimulation in PKR+/+ and −/− MEFs	Western blot	Inhibitor of apoptosis protein-1, -2 and XIAP block the induction of apoptosis by associating with cytosolic regions of death domain containing receptors to block the induction of associated caspases such as caspase 8.	[49,124,136]
	Treatment of CLL patient samples and cell lines and pancreatic cancer cell lines with a pharmacological inhibitor or GSK3β siRNA	RT-PCR/Western blot

^aDescriptive information of the genes and proteins above was taken from the Mendelian Inheritance in Man website available through the National Center for Biotechnology Information (NCBI), National Institutes of Health (NIH).