DNA-damage-inducible transcript 4 (DDIT4) protein also known as protein regulated in development and DNA damage response 1 (REDD1) is a protein that in humans is encoded by the DDIT4 gene. [5] [6]
DNA-damage-inducible transcript 4 (DDIT4) protein also known as protein regulated in development and DNA damage response 1 (REDD1) is a protein that in humans is encoded by the DDIT4 gene. [5] [6]
DDIT4 acts as a negative regulator of mTOR, [7] a serine/threonine kinase that regulates a variety of cellular functions such as growth, proliferation and autophagy. [8] In particular, upregulation of HIF-1 in response to hypoxia upregulates DDIT4, [5] leading to activation of Tsc1/2 via 14–3–3 shuttling [9] and subsequent downregulation of mTOR via Rheb. [10] In addition to hypoxia, DDIT4 expression has also been shown to be activated by DNA damage [11] and energy stress. [12]
Clinical interest in DDIT4 is based primarily on its effect on mTOR, which has been associated with aging [13] and linked with diseases such as tuberous sclerosis, lymphangioleiomyomatosis, [14] diabetes, [13] and cancer. In particular, the overactivation of mTOR in many cancer types [8] has led to the development of mTOR inhibitors for cancer treatment. DDIT4 has begun to receive attention in this regard via the diabetes drug Metformin which has been shown to reduce cancer risk and increase DDIT4 expression. [15]
The Von Hippel–Lindau tumor suppressor also known as pVHL is a protein that, in humans, is encoded by the VHL gene. Mutations of the VHL gene are associated with Von Hippel–Lindau disease.
Tuberous Sclerosis Complex 2 (TSC2), also known as Tuberin, is a protein that in humans is encoded by the TSC2 gene.
DNA damage-inducible transcript 3, also known as C/EBP homologous protein (CHOP), is a pro-apoptotic transcription factor that is encoded by the DDIT3 gene. It is a member of the CCAAT/enhancer-binding protein (C/EBP) family of DNA-binding transcription factors. The protein functions as a dominant-negative inhibitor by forming heterodimers with other C/EBP members, preventing their DNA binding activity. The protein is implicated in adipogenesis and erythropoiesis and has an important role in the cell's stress response.
Protein NDRG1 is a protein that in humans is encoded by the NDRG1 gene.
N-alpha-acetyltransferase 10 (NAA10) also known as NatA catalytic subunit Naa10 and arrest-defective protein 1 homolog A (ARD1A) is an enzyme subunit that in humans is encoded NAA10 gene. Together with its auxiliary subunit Naa15, Naa10 constitutes the NatA complex that specifically catalyzes the transfer of an acetyl group from acetyl-CoA to the N-terminal primary amino group of certain proteins. In higher eukaryotes, 5 other N-acetyltransferase (NAT) complexes, NatB-NatF, have been described that differ both in substrate specificity and subunit composition.
Transcriptional regulator Kaiso is a protein that in humans is encoded by the ZBTB33 gene. This gene encodes a transcriptional regulator with bimodal DNA-binding specificity, which binds to methylated CGCG and also to the non-methylated consensus KAISO-binding site TCCTGCNA. The protein contains an N-terminal POZ/BTB domain and 3 C-terminal zinc finger motifs. It recruits the N-CoR repressor complex to promote histone deacetylation and the formation of repressive chromatin structures in target gene promoters. It may contribute to the repression of target genes of the Wnt signaling pathway, and may also activate transcription of a subset of target genes by the recruitment of catenin delta-2 (CTNND2). Its interaction with catenin delta-1 (CTNND1) inhibits binding to both methylated and non-methylated DNA. It also interacts directly with the nuclear import receptor Importin-α2, which may mediate nuclear import of this protein. Alternatively spliced transcript variants encoding the same protein have been identified.
Eukaryotic translation initiation factor 2-alpha kinase 1 is an enzyme that in humans is encoded by the EIF2AK1 gene.
Calcium-binding and coiled-coil domain-containing protein 1 is a protein that in humans is encoded by the CALCOCO1 gene.
HIG1 domain family member 1A (HIGD1A), also known as hypoglycemia/hypoxia inducible mitochondrial protein1-a (HIMP1-a) and hypoxia induced gene 1 (HIG1), is a protein that in humans is encoded by the HIGD1A gene on chromosome 3. This protein promotes mitochondrial homeostasis and survival of cells under stress and is involved in inflammatory and hypoxia-related diseases, including atherosclerosis, ischemic heart disease, and Alzheimer’s disease, as well as cancer.
WD repeat domain phosphoinositide-interacting protein 2 is a protein that in humans is encoded by the WIPI2 gene.
RCC1 and BTB domain-containing protein 1 is a protein that in humans is encoded by the RCBTB1 gene.
Stannin is a protein that in humans is encoded by the SNN gene.
Activating signal cointegrator 1 complex subunit 3 is a protein that in humans is encoded by the ASCC3 gene.
Myopodin protein, also called Synaptopodin-2 is a protein that in humans is encoded by the SYNPO2 gene. Myopodin is expressed in cardiac, smooth muscle and skeletal muscle, and localizes to Z-disc structures.
DEP domain-containing mTOR-interacting protein (DEPTOR) also known as DEP domain-containing protein 6 (DEPDC6) is a protein that in humans is encoded by the DEPTOR gene.
Sestrin-2 also known as Hi95 is a protein that in humans is encoded by the SESN2 gene.
Tuberous sclerosis proteins 1 and 2, also known as TSC1 (hamartin) and TSC2 (tuberin), form a protein-complex. The encoding two genes are TSC1 and TSC2. The complex is known as a tumor suppressor. Mutations in these genes can cause tuberous sclerosis complex. Depending on the grade of the disease, intellectual disability, epilepsy and tumors of the skin, retina, heart, kidney and the central nervous system can be symptoms.
mTORC1, also known as mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1, is a protein complex that functions as a nutrient/energy/redox sensor and controls protein synthesis.
Human growth and transformation-dependent protein (HGTD-P), also called E2-induced gene 5 protein (E2IG5), is a protein that in humans is encoded by the FAM162A gene on chromosome 3. This protein promotes intrinsic apoptosis in response to hypoxia via interactions with hypoxia-inducible factor-1α (HIF-1α). As a result, it has been associated with cerebral ischemia, myocardial infarction, and various cancers.
DNA-damage-inducible transcript 4 like (DDIT4L) or regulated in development and DNA damage response 2 (REDD2) is a protein that in humans is encoded by the DDIT4L gene. The gene is located on chromosome 4 or chromosome 3 in human or mouse respectively.