Hyperphosphorylation

Hyperphosphorylation occurs when a biochemical with multiple

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

sites is fully saturated. Hyperphosphorylation is one of the signaling mechanisms used by the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

to regulate

mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...

. When these mechanisms fail, developmental problems or

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

are a likely outcome. The mechanism appears to be largely conserved throughout

eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

species. The dynamics of mitosis are similar to a state machine. In a healthy cell, checkpoints between phases permit a new phase to begin only when the previous phase is complete and successful. At these checkpoints, gatekeeper molecules block or allow events, depending on their level of phosphorylation.

Kinases In biochemistry, a kinase () is an enzyme that catalysis, catalyzes the transfer of phosphate groups from High-energy phosphate, high-energy, phosphate-donating molecules to specific Substrate (biochemistry), substrates. This process is known as ...

are responsible for adding

phosphate group In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosphor ...

s and

phosphatases In biochemistry, a phosphatase is an enzyme that uses water to cleave a phosphoric acid monoester into a phosphate ion and an alcohol. Because a phosphatase enzyme catalyzes the hydrolysis of its substrate, it is a subcategory of hydrolases. ...

for removing them.

Cyclin Cyclin is a family of proteins that controls the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes or group of enzymes required for synthesis of cell cycle. Etymology Cyclins were originally disco ...

s are molecules that manage the timing of cell cycle events. Cyclin dependent kinases pair up with cyclins to become operational. Cyclins are named because they are created or destroyed at predetermined points within the cell cycle. Kinase inhibitors add another level of modulation. Kinase inhibitors are grouped into classes and are assigned not very descriptive acronyms. These include INKS for inhibitors of kinase, KIPS for kinase inhibitors and CKIPS for cyclin dependent kinases inhibitors. Scientists have used a variety of tools to unravel the role of hyperphosphorylation. These include the study of knockout genes, the use of antibodies to block receptors on particular molecules, the use of temperature sensitive mutants, and

microarray A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample (e.g. from a tissue). It is a two-dimensional array on a solid substrate—usually a glass slide or silicon t ...

s to monitor the expression of particular genes.

Yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...

are a popular species for study because of the rapid cell cycle. Rb is one of the most studied checkpoint molecules. It is so named because defects in Rb are linked to

retinoblastoma Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and it is almost exclusively fo ...

. In its unphosphorylated state it blocks the transition from G0 or resting state to S or synthesis. It does this in at least 3 ways. It inhibits RNA synthesis, it prevents chromosomes from unwinding and it binds E2F, a factor needed for DNA synthesis. When it is hyperphosphorylated, Rb becomes inactive, releasing bound E2F and allowing phase S to proceed. Wee is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that operates at the G2 to metaphase checkpoint. Wee becomes active if errors occur in the DNA synthesis phase. It blocks entry into metaphase until the problem is resolved. Like Rb, Wee becomes inactive when hyperphosphorylated. In contrast

Mad1 Mad1 is a non-essential protein which in yeast has a function in the spindle assembly checkpoint (SAC). This checkpoint monitors chromosome attachment to spindle microtubules and prevents cells from starting anaphase until the spindle is built up ...

is active when hyperphosphorylated. In its active state it is part of the checkpoint that blocks transition to anaphase.

Cdc2 Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in th ...

, part of the metaphase entry checkpoint, is active depending on the pattern of phosphorylation. {{Protein posttranslational modification Cell biology Signal transduction Post-translational modification Phosphorus Cell cycle