Programmed cell death protein 10 is a protein that in humans is encoded by the PDCD10 gene. [5] [6]
Programmed cell death protein 10 is a protein that in humans is encoded by the PDCD10 gene. [5] [6]
This gene encodes a protein, originally identified in a premyeloid cell line, with similarity to proteins that participate in apoptosis. Three alternative transcripts encoding the same protein, differing only in their 5' UTRs, have been identified for this gene. [6]
Loss of function mutations in PDCD10 result in the onset of Cerebral Cavernous Malformations (CCM) illness. [5] Therefore, this gene is also called CCM3. Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord made of dilated capillary vessels.
CCM3 encodes a protein called Programmed Cell Death 10 (PDCD10). The function of this protein has only recently begun to be understood. PDCD10 has roles in vascular development and VEGF signaling1, [7] apoptosis [8] and functions as part of a larger signaling complex that includes germinal center kinase III,. [9] [10] Specifically, PDCD10 has been shown to interact with RP6-213H19.1, [11] STK25, [11] [12] STRN, [11] STRN3, [11] MOBKL3, [11] CTTNBP2NL, [11] STK24 [11] [12] [13] and FAM40A. [11]
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Abnormal |
| Recessive lethal study | Abnormal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Haematology | Normal |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Skin Histopathology | Normal |
| Eye Histopathology | Normal |
| Salmonella infection | Normal [14] |
| Citrobacter infection | Normal [15] |
| All tests and analysis from [16] [17] |
Model organisms have been used in the study of PDCD10 function. A conditional knockout mouse line, called Pdcd10tm1a(KOMP)Wtsi [18] [19] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. [20] [21] [22]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. [16] [23] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed. [16] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals. [16]
Cerebral cavernous malformation (CCM) is a cavernous hemangioma that arises in the central nervous system. It can be considered to be a variant of hemangioma, and is characterized by grossly large dilated blood vessels and large vascular channels, less well circumscribed, and more involved with deep structures, with a single layer of endothelium and an absence of neuronal tissue within the lesions. These thinly walled vessels resemble sinusoidal cavities filled with stagnant blood. Blood vessels in patients with cerebral cavernous malformations (CCM) can range from a few millimeters to several centimeters in diameter. Most lesions occur in the brain, but any organ may be involved.
Programmed cell death 6-interacting protein also known as ALIX is a protein that in humans is encoded by the PDCD6IP gene.
Krev interaction trapped protein 1 or Cerebral cavernous malformations 1 protein is a protein that in humans is encoded by the KRIT1 gene. This gene contains 16 coding exons and is located on chromosome 7q21.2. Loss of function mutations in KRIT1 result in the onset of cerebral cavernous malformation. Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord made of dilated capillary vessels.
Programmed cell death protein 4 is a protein that in humans is encoded by the PDCD4 gene. It is one of the targets of an oncomiR, MIRN21.
Autophagy related 5 (ATG5) is a protein that, in humans, is encoded by the ATG5 gene located on Chromosome 6. It is an E3 ubi autophagic cell death. ATG5 is a key protein involved in the extension of the phagophoric membrane in autophagic vesicles. It is activated by ATG7 and forms a complex with ATG12 and ATG16L1. This complex is necessary for LC3-I conjugation to PE (phosphatidylethanolamine) to form LC3-II. ATG5 can also act as a pro-apoptotic molecule targeted to the mitochondria. Under low levels of DNA damage, ATG5 can translocate to the nucleus and interact with survivin.
Integrin beta-1-binding protein 1 is a protein that in humans is encoded by the ITGB1BP1 gene.
The CCM2 gene contains 10 coding exons and an alternatively spliced exon 1B. This gene is located on chromosome 7p13 and loss of function mutations on CCM2 lead to the onset of Cerebral Cavernous Malformations (CCM) illness. Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord made of dilated capillary vessels.
Serine/threonine protein kinase MST4, also known as mammalian STE20-like protein kinase 4 (MST-4), is a protein that in humans is encoded by the MST4 gene.
Immunoglobulin-binding protein 1 is a protein that in humans is encoded by the IGBP1 gene.
CTTNBP2 N-terminal-like protein is a protein that in humans is encoded by the CTTNBP2NL gene. It is a substrate for phosphorylation.
Serine/threonine-protein kinase 24 is an enzyme that in humans is encoded by the STK24 gene located in the chromosome 13, band q32.2. It is also known as Mammalian STE20-like protein kinase 3 (MST-3). The protein is 443 amino acids long and its mass is 49 kDa.
Mps one binder kinase activator-like 3 is an enzyme that in humans is encoded by the MOBKL3 gene.
Programmed cell death protein 2 is a protein that in humans is encoded by the PDCD2 gene.
Striatin-3 is a protein that in humans is encoded by the STRN3 gene.
Striatin is a protein that in humans is encoded by the STRN gene.
Serine/threonine-protein kinase 25 is an enzyme that in humans is encoded by the STK25 gene.
Sarcolemmal membrane-associated protein is a protein that in humans is encoded by the SLMAP gene.
TRAF3-interacting JNK-activating modulator is a protein that in humans is encoded by the TRAF3IP3 gene.
Cortactin-binding protein 2 is a protein that in humans is encoded by the CTTNBP2 gene.
Cavernous hemangioma, also called cavernous angioma, venous malformation, or cavernoma, is a type of venous malformation due to endothelial dysmorphogenesis from a lesion which is present at birth. A cavernoma in the brain is called a cerebral cavernous malformation or CCM. Despite its designation as a hemangioma, a cavernous hemangioma is not a tumor as it does not display endothelial hyperplasia. The abnormal tissue causes a slowing of blood flow through the cavities, or "caverns". The blood vessels do not form the necessary junctions with surrounding cells, and the structural support from the smooth muscle is hindered, causing leakage into the surrounding tissue. It is the leakage of blood, referred to as hemorrhage, that causes a variety of symptoms known to be associated with the condition.