Programmed cell death

Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses 50 to 70 billion cells each day to apoptosis. For the average human child between 8 and 14 years old, each day the approximate loss is 20 to 30 billion cells.

thumb|right|A Diagram of the process of autophagy, which produces the structures autophagosomes (AP), and [[autolysosomes (AL)B Electron micrograph of autophagic structures AP and AL in the fat body of a fruit fly larvaC Fluorescently labeled autophagosomes AP in liver cells of starved mice]]

p53, also known as tumor protein p53, TP53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often spoken of as, a single protein) are crucial in vertebrates, where they prevent cancer formation. As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation. Hence TP53 is classified as a tumor suppressor gene.

cellular process

mammalian protein found in Homo sapiens

Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. As of 2009, there are 12 confirmed caspases in humans and 10 in mice, carrying out a variety of cellular functions.

450px|thumb|Mechanism of NF-κB action. The classic "canonical" NF-κB complex is a heterodimer of p50 and RelA, as shown. NF-κB waits for activation in the cytosol, complexed with the inhibitory protein IκBα. Various extracellular signals can enter the cell via membrane receptors and activate the enzyme [[IκB kinase (IKK). IKK, in turn, phosphorylates the IκBα protein, which results in ubiquitination, dissociation of IκBα from NF-κB, and eventual degradation of IκBα by the proteasome. The activated NF-κB is then translocated into the nucleus where it binds to specific sequences of DNA called re

biological process

Perforin-1 (PRF) is a pore-forming protein encoded in humans by the PRF1 gene. It is stored in the secretory granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, collectively known as cytotoxic lymphocytes (CLs). Upon activation, these cells release perforin to form pores in the membranes of target cells, enabling the entry of granzymes that trigger apoptosis. Perforin is therefore a central effector molecule of the immune system, essential for the elimination of virus-infected and transformed cells. Mutations in PRF1 that impair perforin expression or function are associa

Bcl-2, encoded in humans by the BCL2 gene, is the founding member of the Bcl-2 family of regulator proteins. BCL2 blocks programmed cell death (apoptosis) while other BCL2 family members can either inhibit or induce it. It was the first apoptosis regulator identified in any organism.

Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.

Granzymes are serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death (apoptosis) in the target cell, thus eliminating cells that have become cancerous or are infected with viruses or bacteria. Granzymes also kill bacteria and inhibit viral replication. In NK cells and T cells, granzymes are packaged in cytotoxic granules along with perforin. Granzymes can also be detected in the rough endoplasmic reticulum, golgi complex, and the trans-golgi reticulum. The contents of the cytotoxic granules function to permit

thumb|300px|Apoptosis Karyorrhexis (from Greek κάρυον karyon, "kernel, seed, nucleus," and ῥῆξις rhexis, "bursting") is the destructive fragmentation of the cell nucleus that occurs in a dying cell. It is characterized by the breakdown of the nuclear envelope and the dispersal of condensed chromatin into the cytoplasm. The process is usually preceded by pyknosis (irreversible chromatin condensation) and followed by karyolysis (enzymatic dissolution of chromatin). It may occur during programmed cell death (apoptosis), cellular senescence, or necrosis.

Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.

thumb|right|350px|Morphological characteristics of karyolysis and other forms of nuclear destruction. Karyolysis (from Greek κάρυον karyon—"kernel, seed, or nucleus", and λύσις lysis from λύειν lyein, "to separate") is the complete dissolution of chromatin in a dying cell caused by enzymatic degradation through endonucleases. Following karyolysis, the entire cell typically stains uniformly with eosin. Karyolysis represents the final step in the process of necrosis, a form of cellular injury in which living tissue undergoes irreversible damage through premature cell death. Unlike apoptosis, whi

thumb|275px|Apoptosis

mammalian protein found in Homo sapiens

protein-coding gene in the species Homo sapiens

thumb|alt=3D structure of the human apoptosome-CARD complex.|3D structure of the human apoptosome-CARD complex. blue: apoptosome platform; magenta: CARD disk

mammalian protein found in Homo sapiens

Pyroptosis is a highly inflammatory form of lytic programmed cell death that occurs most frequently upon infection with intracellular pathogens and forms part of the antimicrobial response. This process promotes the rapid clearance of various bacterial, viral, fungal and protozoan infections by removing intracellular replication niches and enhancing the host's defensive responses. Pyroptosis can take place in immune cells and is also reporte d to occur in keratinocytes and some epithelial cells.

Ferroptosis (also known as oxytosis) is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides. Ferroptosis is biochemically, genetically, and morphologically distinct from other forms of regulated cell death such as apoptosis and necroptosis. Oxytosis/ferroptosis can be initiated by the failure of the glutathione-dependent antioxidant defenses, resulting in unchecked lipid peroxidation and eventual cell death. Lipophilic antioxidants and iron chelators can prevent ferroptotic cell death.

FAS-associated death domain protein, also called MORT1, is encoded by the FADD gene on the 11q13.3 region of chromosome 11 in humans.

InterPro Family

molecular biology method used to detect DNA fragmentation

InterPro Family

X-linked inhibitor of apoptosis protein (XIAP), also known as inhibitor of apoptosis protein 3 (IAP3) and baculoviral IAP repeat-containing protein 4 (BIRC4), is a protein that stops apoptotic cell death. In humans, this protein (XIAP) is produced by a gene named XIAP gene located on the X chromosome.

thumb | right | Mechanisms of resistance to anoikisAnoikis is a form of programmed cell death that occurs in anchorage-dependent cells when they detach from the surrounding extracellular matrix (ECM). Usually cells stay close to the tissue to which they belong since the communication between proximal cells as well as between cells and ECM provide essential signals for growth or survival. When cells are detached from the ECM, there is a loss of normal cell–matrix interactions, and they may undergo anoikis. However, metastatic tumor cells may escape from anoikis and invade other organs.

gene causing apoptosis

protein-coding gene in the species Homo sapiens

protein-coding gene in the species Homo sapiens

InterPro Domain

hypothesis that aging is caused by accumulated DNA damage

protein-coding gene in the species Homo sapiens

bulge in the plasma membrane of a cell

mammalian protein found in Homo sapiens

Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5) is a member of MAP kinase family and as such a part of mitogen-activated protein kinase pathway. It activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases in a Raf-independent fashion in response to an array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. ASK1 has been found to be involved in cancer, diabetes, rheumatoid arthritis, cardiovascular and neurodegenerative diseases.

IKK-β also known as inhibitor of nuclear factor kappa-B kinase subunit beta is a protein that in humans is encoded by the IKBKB (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta) gene.