Anaphase
Anaphase-Promoting Complex-Cyclosome
Ubiquitin-Protein Ligase Complexes
Cdc20 Proteins
Cdh1 Proteins
Clostridium botulinum type G
Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome
Cell Cycle Proteins
Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome
Spindle Apparatus
Neurospora
Cyclin B
F-Box Proteins
Genes, APC
Metaphase
Ligases
M Phase Cell Cycle Checkpoints
Cyclin A2
Apc5 Subunit, Anaphase-Promoting Complex-Cyclosome
Mad2 Proteins
Cyclin B1
Ubiquitin-Protein Ligases
Cell Cycle
Prometaphase
CDC2 Protein Kinase
HeLa Cells
Meiosis
Ubiquitination
Geminin
Schizosaccharomyces pombe Proteins
Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome
Cyclin A
Saccharomyces cerevisiae Proteins
Protein-Serine-Threonine Kinases
Molecular Sequence Data
Schizosaccharomyces
Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome
Separase
Amino Acid Sequence
Nocodazole
Mutation
Nuclear Proteins
Telophase
Aurora Kinases
Chromatids
Proto-Oncogene Proteins c-mos
Xenopus Proteins
G1 Phase
Genes, cdc
Protein Binding
Oocytes
Protein Subunits
Microtubules
Ubiquitin
Ubiquitin-Conjugating Enzymes
Xenopus
Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome
SKP Cullin F-Box Protein Ligases
Saccharomyces cerevisiae
Ubiquitins
Kinetochores
Proteasome Endopeptidase Complex
Phosphorylation
RNA Interference
Chromosomes
Recombinant Fusion Proteins
S Phase
Amino Acid Motifs
Calcium-Binding Proteins
Drosophila Proteins
Models, Biological
G2 Phase
Protein Kinases
Substrate Specificity
Centromere
Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome
Carrier Proteins
Repressor Proteins
Adenomatous Polyposis Coli Protein
Cadherins
Protein Processing, Post-Translational
Cyclins
Drosophila
RNA, Small Interfering
Protein Stability
Chromosomal Proteins, Non-Histone
Macromolecular Substances
Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome
Cyclin-Dependent Kinases
Base Sequence
Microtubule-Associated Proteins
Sequence Homology, Amino Acid
Kinesin
Prophase
Bivalvia
Endoreduplication
Endopeptidases
Tubulin
Interphase
Aurora Kinase B
Protein Structure, Tertiary
Spermatocytes
Cell Nucleus
Cell Division
Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome
Centrosome
Sequence Alignment
Microscopy, Fluorescence
Adenomatous Polyposis Coli
Binding Sites
Embryo, Nonmammalian
Saccharomycetales
Cloning, Molecular
Macropodidae
Two-Hybrid System Techniques
Chromosomes, Fungal
Caenorhabditis elegans
Signal Transduction
Enzyme Activation
Cell Cycle Checkpoints
Dyneins
Chromosomes, Human
Nondisjunction, Genetic
Escherichia coli
Proteolysis
Multiprotein Complexes
Protein Conformation
Gene Expression Regulation, Fungal
Fluorescent Antibody Technique
Phosphoprotein Phosphatases
DNA-Binding Proteins
Green Fluorescent Proteins
Cell Nucleolus
Cells, Cultured
Electrophoresis, Polyacrylamide Gel
Proton-Translocating ATPases
Protein Phosphatase 2
Models, Molecular
DNA, Catenated
Phenotype
Potoroidae
RNA, Messenger
Protein Tyrosine Phosphatases
Chromosomal Instability
Protein C
Cytoskeletal Proteins
Dipodomys
Mutagenesis, Site-Directed
Aneuploidy
Internal Medicine
Protein Transport
Sister Chromatid Exchange
Blotting, Western
Microscopy, Video
Diptera
Adenosine Triphosphatases
Mutagenesis
Luminescent Proteins
DNA Primers
Drosophila melanogaster
DNA
Microinjections
Cytoplasm
Gene Deletion
Transfection
Peptide Fragments
Proto-Oncogene Proteins
Vaccines, Subunit
Nuclear Matrix-Associated Proteins
beta Catenin
DNA, Complementary
Chromatin
Vacuolar Proton-Translocating ATPases
Salamandridae
Xenopus laevis
Antigen-Presenting Cells
Transcription, Genetic
Precipitin Tests
Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex. (1/7)
The anaphase-promoting complex/cyclosome (APC) is a ubiquitin-protein ligase whose activity is essential for progression through mitosis. The vertebrate APC is thought to be composed of 8 subunits, whereas in budding yeast several additional APC-associated proteins have been identified, including a 33-kDa protein called Doc1 or Apc10. Here, we show that Doc1/Apc10 is a subunit of the yeast APC throughout the cell cycle. Mutation of Doc1/Apc10 inactivates the APC without destabilizing the complex. An ortholog of Doc1/Apc10, which we call APC10, is associated with the APC in different vertebrates, including humans and frogs. Biochemical fractionation experiments and mass spectrometric analysis of a component of the purified human APC show that APC10 is a genuine APC subunit whose cellular levels or association with the APC are not cell cycle-regulated. We have further identified an APC10 homology region, which we propose to call the DOC domain, in several protein sequences that also contain either cullin or HECT domains. Cullins are present in several ubiquitination complexes including the APC, whereas HECT domains represent the catalytic core of a different type of ubiquitin-protein ligase. DOC domains may therefore be important for reactions catalyzed by several types of ubiquitin-protein ligases. (+info)Identification of human APC10/Doc1 as a subunit of anaphase promoting complex. (2/7)
Anaphase-promoting complex or cyclosome (APC) is a ubiquitin ligase which specifically targets mitotic regulatory factors such as Pds1/Cut2 and cyclin B. Identification of the subunits of multiprotein complex APC in several species revealed the highly conserved composition of APC from yeast to human. It has been reported, however, that vertebrate APC is composed of at least eight subunits, APC1 to APC8, while budding yeast APC is constituted of at least 12 components, Apc1 to Apc13. It has not yet been clearly understood whether additional components found in budding yeast, Apc9 to Apc13, are actually composed of mammalian APC. Here we isolated and characterized human APC10/Doc1, and found that APC10/Doc1 binds to APC core subunits throughout the cell cycle. Further, it was found that APC10/Doc1 is localized in centrosomes and mitotic spindles throughout mitosis, while it is also localized in kinetochores from prophase to anaphase and in midbody in telophase and cytokinesis. These results strongly support the notion that human APC10/Doc1 may be one of the APC core subunits rather than the transiently associated regulatory factor. (+info)Doc1 mediates the activity of the anaphase-promoting complex by contributing to substrate recognition. (3/7)
The anaphase-promoting complex (APC) is a multisubunit E3 ubiquitin ligase that targets specific cell cycle-related proteins for degradation, regulating progression from metaphase to anaphase and exit from mitosis. The APC is regulated by binding of the coactivator proteins Cdc20p and Cdh1p, and by phosphorylation. We have developed a purification strategy that allowed us to purify the budding yeast APC to near homogeneity and identify two novel APC-associated proteins, Swm1p and Mnd2p. Using an in vitro ubiquitylation system and a native gel binding assay, we have characterized the properties of wild-type and mutant APC. We show that both the D and KEN boxes contribute to substrate recognition and that coactivator is required for substrate binding. APC lacking Apc9p or Doc1p/Apc10 have impaired E3 ligase activities. However, whereas Apc9p is required for structural stability and the incorporation of Cdc27p into the APC complex, Doc1p/Apc10 plays a specific role in substrate recognition by APC-coactivator complexes. These results imply that Doc1p/Apc10 may play a role to regulate the binding of specific substrates, similar to that of the coactivators. (+info)The APC subunit Doc1 promotes recognition of the substrate destruction box. (4/7)
BACKGROUND: Accurate chromosome segregation during mitosis requires the coordinated destruction of the mitotic regulators securin and cyclins. The anaphase-promoting complex (APC) is a multisubunit ubiquitin-protein ligase that catalyzes the polyubiquitination of these and other proteins and thereby promotes their destruction. How the APC recognizes its substrates is not well understood. In mitosis, the APC activator Cdc20 binds to the APC and is thought to recruit substrates by interacting with a conserved target protein motif called the destruction box. A related protein, called Cdh1, performs a similar function during G1. Recent evidence, however, suggests that the core APC subunit Doc1 also contributes to substrate recognition. RESULTS: To better understand the mechanism by which Doc1 promotes substrate binding to the APC, we generated a series of point mutations in Doc1 and analyzed their effects on the processivity of substrate ubiquitination. Mutations that reduce Doc1 function fall into two classes that define spatially and functionally distinct regions of the protein. One region, which includes the carboxy terminus, anchors Doc1 to the APC but does not influence substrate recognition. The other region, located on the opposite face of Doc1, is required for Doc1 to enhance substrate binding to the APC. Importantly, stimulation of binding by Doc1 also requires that the substrate contain an intact destruction box. Cells carrying DOC1 mutations that eliminate substrate recognition delay in mitosis with high levels of APC substrates. CONCLUSIONS: Doc1 contributes to recognition of the substrate destruction box by the APC. This function of Doc1 is necessary for efficient substrate proteolysis in vivo. (+info)Structures of APC/C(Cdh1) with substrates identify Cdh1 and Apc10 as the D-box co-receptor. (5/7)
(+info)Spindle assembly requires complete disassembly of spindle remnants from the previous cell cycle. (6/7)
(+info)A novel yeast screen for mitotic arrest mutants identifies DOC1, a new gene involved in cyclin proteolysis. (7/7)
B-type cyclins are rapidly degraded at the transition between metaphase and anaphase and their ubiquitin-mediated proteolysis is required for cells to exit mitosis. We used a novel enrichment to isolate new budding mutants that arrest the cell cycle in mitosis. Most of these mutants lie in the CDC16, CDC23, and CDC27 genes, which have already been shown to play a role in cyclin proteolysis and encode components of a 20S complex (called the cyclosome or anaphase promoting complex) that ubiquitinates mitotic cyclins. We show that mutations in CDC26 and a novel gene, DOC1, also prevent mitotic cyclin proteolysis. Mutants in either gene arrest as large budded cells with high levels of the major mitotic cyclin (Clb2) protein at 37 degrees C and cannot degrade Clb2 in G1-arrested cells. Cdc26 associates in vivo with Doc1, Cdc16, Cdc23, and Cdc27. In addition, the majority of Doc1 cosediments at 20S with Cdc27 in a sucrose gradient, indicating that Cdc26 and Doc1 are components of the anaphase promoting complex. (+info)The APC gene is a tumor suppressor gene that helps regulate cell growth and prevent the formation of tumors. Mutations in the APC gene can cause the development of adenomas, which are precancerous growths that can eventually become colon cancer if left untreated.
APC mutations can be inherited from one's parents or can occur spontaneously. The risk of developing colorectal cancer is increased in people with an APC mutation, and regular screening and monitoring is recommended to detect and remove any precancerous growths before they become cancerous.
Symptoms of APC may include abdominal pain, diarrhea, rectal bleeding, and weight loss. Treatment for APC typically involves removal of the affected portion of the colon and rectum, followed by ongoing monitoring and screening to detect any recurrences.
In summary, adenomatous polyposis coli (APC) is a genetic condition that increases the risk of developing colorectal cancer and other cancers. It is caused by mutations in the APC gene and can be inherited or acquired spontaneously. Symptoms may include abdominal pain, diarrhea, rectal bleeding, and weight loss, and treatment typically involves removal of the affected portion of the colon and rectum, followed by ongoing monitoring and screening.
There are several types of genetic nondisjunction, including:
1. Robertsonian translocation: This type of nondisjunction involves the exchange of genetic material between two chromosomes, resulting in a mixture of genetic information that can lead to developmental abnormalities.
2. Turner syndrome: This is a rare condition that occurs when one X chromosome is missing or partially present, leading to physical and developmental abnormalities in females.
3. Klinefelter syndrome: This condition occurs when an extra X chromosome is present, leading to physical and developmental abnormalities in males.
4. Trisomy 13: This condition occurs when there are three copies of chromosome 13, leading to severe developmental and physical abnormalities.
5. Trisomy 18: This condition occurs when there are three copies of chromosome 18, leading to severe developmental and physical abnormalities.
Genetic nondisjunction can be caused by various factors, including genetic mutations, errors during meiosis, or exposure to certain chemicals or radiation. It can be diagnosed through cytogenetic analysis, which involves studying the chromosomes of cells to identify any abnormalities.
Treatment for genetic nondisjunction depends on the specific type and severity of the condition. In some cases, no treatment is necessary, while in others, medication or surgery may be recommended. Prenatal testing can also be done to detect genetic nondisjunction before birth.
In summary, genetic nondisjunction is a chromosomal abnormality that occurs during meiosis and can lead to developmental and physical abnormalities. It can be caused by various factors and diagnosed through cytogenetic analysis. Treatment depends on the specific type and severity of the condition, and prenatal testing is available to detect genetic nondisjunction before birth.
Causes of Chromosomal Instability:
1. Genetic mutations: Mutations in genes that regulate the cell cycle or chromosome segregation can lead to CIN.
2. Environmental factors: Exposure to certain environmental agents such as radiation and certain chemicals can increase the risk of developing CIN.
3. Errors during DNA replication: Mistakes during DNA replication can also lead to CIN.
Types of Chromosomal Instability:
1. Aneuploidy: Cells with an abnormal number of chromosomes, either more or fewer than the normal diploid number (46 in humans).
2. Structural changes: Deletions, duplications, inversions, translocations, and other structural changes can occur in the chromosomes.
3. Unstable chromosome structures: Chromosomes with abnormal shapes or structures, such as telomere shortening, centromere instability, or chromosome breaks, can also lead to CIN.
Effects of Chromosomal Instability:
1. Cancer: CIN can increase the risk of developing cancer by disrupting normal cellular processes and leading to genetic mutations.
2. Aging: CIN can contribute to aging by shortening telomeres, which are the protective caps at the ends of chromosomes that help maintain their stability.
3. Neurodegenerative diseases: CIN has been implicated in the development of certain neurodegenerative diseases such as Alzheimer's and Parkinson's.
4. Infertility: CIN can lead to infertility by disrupting normal meiotic recombination and chromosome segregation during gametogenesis.
Detection and Diagnosis of Chromosomal Instability:
1. Karyotyping: This is a technique used to visualize the entire set of chromosomes in a cell. It can help identify structural abnormalities such as deletions, duplications, or translocations.
2. Fluorescence in situ hybridization (FISH): This technique uses fluorescent probes to detect specific DNA sequences or proteins on chromosomes. It can help identify changes in chromosome structure or number.
3. Array comparative genomic hybridization (aCGH): This technique compares the genetic material of a sample to a reference genome to identify copy number changes.
4. Next-generation sequencing (NGS): This technique can identify point mutations and other genetic changes in DNA.
Treatment and Management of Chromosomal Instability:
1. Cancer treatment: Depending on the type and stage of cancer, treatments such as chemotherapy, radiation therapy, or surgery may be used to eliminate cancer cells with CIN.
2. Prenatal testing: Pregnant women with a family history of CIN can undergo prenatal testing to detect chromosomal abnormalities in their fetuses.
3. Genetic counseling: Individuals with a family history of CIN can consult with a genetic counselor to discuss risk factors and potential testing options.
4. Lifestyle modifications: Making healthy lifestyle choices such as maintaining a balanced diet, exercising regularly, and not smoking can help reduce the risk of developing cancer and other diseases associated with CIN.
In conclusion, chromosomal instability is a common feature of many human diseases, including cancer, and can be caused by a variety of factors. The diagnosis and management of CIN require a multidisciplinary approach that includes cytogenetic analysis, molecular diagnostics, and clinical evaluation. Understanding the causes and consequences of CIN is crucial for developing effective therapies and improving patient outcomes.
There are several types of aneuploidy, including:
1. Trisomy: This is the presence of an extra copy of a chromosome. For example, Down syndrome is caused by an extra copy of chromosome 21 (trisomy 21).
2. Monosomy: This is the absence of a chromosome.
3. Mosaicism: This is the presence of both normal and abnormal cells in the body.
4. Uniparental disomy: This is the presence of two copies of a chromosome from one parent, rather than one copy each from both parents.
Aneuploidy can occur due to various factors such as errors during cell division, exposure to certain chemicals or radiation, or inheritance of an abnormal number of chromosomes from one's parents. The risk of aneuploidy increases with age, especially for women over the age of 35, as their eggs are more prone to errors during meiosis (the process by which egg cells are produced).
Aneuploidy can be diagnosed through various methods such as karyotyping (examining chromosomes under a microscope), fluorescence in situ hybridization (FISH) or quantitative PCR. Treatment for aneuploidy depends on the underlying cause and the specific health problems it has caused. In some cases, treatment may involve managing symptoms, while in others, it may involve correcting the genetic abnormality itself.
In summary, aneuploidy is a condition where there is an abnormal number of chromosomes present in a cell, which can lead to various developmental and health problems. It can occur due to various factors and can be diagnosed through different methods. Treatment depends on the underlying cause and the specific health problems it has caused.
Types of Intestinal Neoplasms:
1. Adenomas: These are benign tumors that grow on the inner lining of the intestine. They can become malignant over time if left untreated.
2. Carcinomas: These are malignant tumors that develop in the inner lining of the intestine. They can be subdivided into several types, including colon cancer and rectal cancer.
3. Lymphoma: This is a type of cancer that affects the immune system and can occur in the intestines.
4. Leiomyosarcomas: These are rare malignant tumors that develop in the smooth muscle layers of the intestine.
Causes and Risk Factors:
The exact cause of intestinal neoplasms is not known, but several factors can increase the risk of developing these growths. These include:
1. Age: The risk of developing intestinal neoplasms increases with age.
2. Family history: Having a family history of colon cancer or other intestinal neoplasms can increase the risk of developing these growths.
3. Inflammatory bowel disease: People with inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, are at higher risk of developing intestinal neoplasms.
4. Genetic mutations: Certain genetic mutations can increase the risk of developing intestinal neoplasms.
5. Diet and lifestyle factors: A diet high in fat and low in fiber, as well as lack of physical activity, may increase the risk of developing intestinal neoplasms.
Symptoms:
Intestinal neoplasms can cause a variety of symptoms, including:
1. Abdominal pain or discomfort
2. Changes in bowel habits, such as diarrhea or constipation
3. Blood in the stool
4. Weight loss
5. Fatigue
6. Loss of appetite
Diagnosis:
To diagnose intestinal neoplasms, a doctor may perform several tests, including:
1. Colonoscopy: A colonoscope is inserted through the rectum and into the colon to visualize the inside of the colon and detect any abnormal growths.
2. Biopsy: A small sample of tissue is removed from the colon and examined under a microscope for cancer cells.
3. Imaging tests: Such as X-rays, CT scans, or MRI scans to look for any abnormalities in the colon.
4. Blood tests: To check for certain substances in the blood that are associated with intestinal neoplasms.
Treatment:
The treatment of intestinal neoplasms depends on the type and location of the growth, as well as the stage of the cancer. Treatment options may include:
1. Surgery: To remove the tumor and any affected tissue.
2. Chemotherapy: To kill any remaining cancer cells with drugs.
3. Radiation therapy: To kill cancer cells with high-energy X-rays or other forms of radiation.
4. Targeted therapy: To use drugs that target specific molecules on cancer cells to kill them.
5. Immunotherapy: To use drugs that stimulate the immune system to fight cancer cells.
Prognosis:
The prognosis for intestinal neoplasms depends on several factors, including the type and stage of the cancer, the location of the growth, and the effectiveness of treatment. In general, early detection and treatment improve the prognosis, while later-stage cancers have a poorer prognosis.
Complications:
Intestinal neoplasms can cause several complications, including:
1. Obstruction: The tumor can block the normal flow of food through the intestine, leading to abdominal pain and other symptoms.
2. Bleeding: The tumor can cause bleeding in the intestine, which can lead to anemia and other complications.
3. Perforation: The tumor can create a hole in the wall of the intestine, leading to peritonitis (inflammation of the lining of the abdomen) and other complications.
4. Metastasis: The cancer cells can spread to other parts of the body, such as the liver or lungs, and cause further complications.
5. Malnutrition: The tumor can make it difficult for the body to absorb nutrients, leading to malnutrition and other health problems.
Prevention:
There is no sure way to prevent intestinal neoplasms, but there are several steps that may help reduce the risk of developing these types of cancer. These include:
1. Avoiding known risk factors: Avoiding known risk factors such as smoking, excessive alcohol consumption, and a diet high in processed meat can help reduce the risk of developing intestinal neoplasms.
2. Maintaining a healthy diet: Eating a balanced diet that is high in fruits, vegetables, and whole grains can help keep the intestines healthy and may reduce the risk of cancer.
3. Exercise regularly: Regular exercise can help maintain a healthy weight, improve digestion, and may reduce the risk of developing intestinal neoplasms.
4. Managing chronic conditions: Managing chronic conditions such as inflammatory bowel disease, diabetes, and obesity can help reduce the risk of developing intestinal neoplasms.
5. Screening tests: Regular screening tests such as colonoscopy, CT scan, or barium enema can help detect precancerous polyps or early-stage cancer, allowing for early treatment and prevention of advanced disease.
Early detection and diagnosis are crucial for effective treatment and survival rates for intestinal neoplasms. If you have any of the risk factors or symptoms mentioned above, it is essential to consult a doctor as soon as possible. A thorough examination and diagnostic tests can help determine the cause of your symptoms and recommend appropriate treatment.
CDC27
CDC16
ANAPC7
ANAPC5
ANAPC2
Anaphase-promoting complex
ANAPC4
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NDF-RT Code NDF-RT Name
Pesquisa | Prevenção e Controle de Câncer
NEW (2014) MESH HEADINGS WITH SCOPE NOTES (UNIT RECORD FORMAT; 7/29/2013
Anaphase-Promoting Complex-Cyclosome | Profiles RNS
DeCS 2014 - Novos termos
DeCS 2014 - Novos termos
TERM
DeCS 2014 - Novos termos
DeCS 2014 - Novos termos
DeCS 2014 - Novos termos
DeCS 2014 - Novos termos
DeCS 2014 - Novos termos
DeCS 2014 - Novos termos
and
Cell Cycle Pr1
- HN - 2014 FX - Ammonia MH - Anaphase-Promoting Complex-Cyclosome UI - D064173 MN - D8.811.464.938.750.92 MN - D12.776.167.24 MS - An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. (nih.gov)
Cdc201
- It binds the Apc2 subunit, which is a part of the catalytic core, and interacts with coactivators Cdh1 or Cdc20 to recruit substrates to the complex. (nih.gov)