AKNA is a protein that in humans is encoded by the AKNA gene. The protein is an AT-hook transcription factor which contains an AT-hook binding motif. The protein is expressed as different isoforms. AKNA is known to upregulate expression of the receptor CD40 and its ligand CD40L/CD154. [5] [6]
AKNA is an essential part in the construction, organization, and proliferation of the centrosomal microtubules in order to maintain the neural stem cells during the process of neurogenesis. [7] [8] Due to these functions AKNA plays in the centrosomal microtubules it also has an active role in delamination during the formation of the subventricular zone, and the regulation of the amount of access provided to cells in this zone. [7] [9] Furthermore, because of AKNA's role in the centrosomal microtubules it also plays a part in the management of the modification of epithelial cells losing their polarity and attachment, and transforming into the mobile mesenchymal stem cells, epithelial-mesenchymal transition (EMT). [5] [9] This occurs because the alongside the increase in centrosomal microtubules both nucleation factors and minus end stabilizers are also increasing, causing the apical endfoot to have its constriction regulated because this affects the microtubules found at adherens junctions. [5] [9] [10]
AKNA derives its name from the word "mother" in Inuit and Mayan language, and it's link to their mythology. [11] For in Inuit and Mayan culture AKNA is the "goddess of fertility and childbirth". [11] This connection is made from the observations of what occurs to mice that are missing the AKNA protein. In mice lacking AKNA their body very rapidly enters an increasing weakened state, very similarly to as if they did not have a mother to support them, and are not likely to live longer than 10 day's. [11]
The AKNA protein in humans has been found to be associated with cervical cancer. This is due to it being located on the 9q32 chromosome, in the FRA9E region. It is not uncommon for this chromosome to play a role in neoplasm and inflammatory diseases because how frequently it undergoes loss of function. [11] [12] [13]
T-box transcription factor T, also known as Brachyury protein, is encoded for in humans by the TBXT gene. Brachyury functions as a transcription factor within the T-box family of genes. Brachyury homologs have been found in all bilaterian animals that have been screened, as well as the freshwater cnidarian Hydra.
Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene.
Forkhead box protein C2 (FOXC2) also known as forkhead-related protein FKHL14 (FKHL14), transcription factor FKH-14, or mesenchyme fork head protein 1 (MFH1) is a protein that in humans is encoded by the FOXC2 gene. FOXC2 is a member of the fork head box (FOX) family of transcription factors.
Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the AURKA gene.
Cripto is an EGF-CFC or epidermal growth factor-CFC, which is encoded by the Cryptic family 1 gene. Cryptic family protein 1B is a protein that in humans is encoded by the CFC1B gene. Cryptic family protein 1B acts as a receptor for the TGF beta signaling pathway. It has been associated with the translation of an extracellular protein for this pathway. The extracellular protein which Cripto encodes plays a crucial role in the development of left and right division of symmetry.
High-mobility group AT-hook 2, also known as HMGA2, is a protein that, in humans, is encoded by the HMGA2 gene.
Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the RHOA gene. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. It acts upon several effectors. Among them, ROCK1 and DIAPH1 are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billion years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation.
Protein C-ets-1 is a protein that in humans is encoded by the ETS1 gene. The protein encoded by this gene belongs to the ETS family of transcription factors.
Kruppel-like factor 4 is a member of the KLF family of zinc finger transcription factors, which belongs to the relatively large family of SP1-like transcription factors. KLF4 is involved in the regulation of proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including colorectal cancer. It has three C2H2-zinc fingers at its carboxyl terminus that are closely related to another KLF, KLF2. It has two nuclear localization sequences that signals it to localize to the nucleus. In embryonic stem cells (ESCs), KLF4 has been demonstrated to be a good indicator of stem-like capacity. It is suggested that the same is true in mesenchymal stem cells (MSCs).
Forkhead box C1, also known as FOXC1, is a protein which in humans is encoded by the FOXC1 gene.
Zinc finger protein SNAI1 is a protein that in humans is encoded by the SNAI1 gene. Snail is a family of transcription factors that promote the repression of the adhesion molecule E-cadherin to regulate epithelial to mesenchymal transition (EMT) during embryonic development.
Zinc finger E-box-binding homeobox 1 is a protein that in humans is encoded by the ZEB1 gene.
Forkhead box protein M1 is a protein that in humans is encoded by the FOXM1 gene. The protein encoded by this gene is a member of the FOX family of transcription factors. Its potential as a target for future cancer treatments led to it being designated the 2010 Molecule of the Year.
Zinc finger protein SNAI2 is a transcription factor that in humans is encoded by the SNAI2 gene. It promotes the differentiation and migration of certain cells and has roles in initiating gastrulation.
Ninein is a protein that in humans is encoded by the NIN gene. Ninein, together with its paralog Ninein-like protein is one of the proteins important for centrosomal function. This protein is important for positioning and anchoring the microtubules minus-ends in epithelial cells. Localization of this protein to the centrosome requires three leucine zippers in the central coiled-coil domain. Multiple alternatively spliced transcript variants that encode different isoforms have been reported.
ETS homologous factor is a protein that in humans is encoded by the EHF gene. This gene encodes a protein that belongs to an ETS transcription factor subfamily characterized by epithelial-specific expression (ESEs). The encoded protein acts as a transcriptional repressor and may be associated with asthma susceptibility. This protein may be involved in epithelial differentiation and carcinogenesis.
Krueppel-like factor 8 is a protein that in humans is encoded by the KLF8 gene. KLF8 belongs to the family of KLF protein. KLF8 is activated by KLF1 along with KLF3 while KLF3 represses KLF8.
Forkhead box protein N1 is a protein that in humans is encoded by the FOXN1 gene.
Cadherin-1 or Epithelial cadherin (E-cadherin), is a protein that in humans is encoded by the CDH1 gene. Mutations are correlated with gastric, breast, colorectal, thyroid, and ovarian cancers. CDH1 has also been designated as CD324. It is a tumor suppressor gene.
E74 like ETS transcription factor 3 is a protein that in humans is encoded by the ELF3 gene.