Pituitary tumor-transforming gene 1 protein-interacting protein (PTTG1), also known as PTTG1-binding factor (PBF), is a poorly characterised

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''PTTG1IP''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

located within the chromosomal region 21q22.3.

Structure

The encoded protein is composed of 180 amino acids and has a predicted molecular mass of 22

kDa The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...

. The peptide sequence shares no significant homology with any other human proteins but is highly conserved across a wide diversity of animal species, suggesting both unique function and evolutionary importance. Initial protein prediction studies suggested that PTTG1IP was a cell surface

glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

, however, the recent identification of a

nuclear localisation signal A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysin ...

(NLS) suggests that it may have a role both in the cytoplasm and as a nuclear protein.

Function

Although PTTG1IP is ubiquitously expressed in normal human tissues, its exact function remains elusive. It has been shown to directly interact with the human

securin Securin is a protein involved in control of the metaphase-anaphase transition and anaphase onset. Following bi-orientation of chromosome pairs and inactivation of the spindle checkpoint system, the underlying regulatory system, which includes securi ...

and

proto-oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

, PTTG1, thus facilitating its nuclear translocation and the subsequent transcriptional activation of

basic fibroblast growth factor Fibroblast growth factor 2 (FGF-2), also known as basic fibroblast growth factor (bFGF) and FGF-β, is a growth factor and signaling protein encoded by the ''FGF2'' gene. It binds to and exerts effects via specific fibroblast growth factor recept ...

(bFGF) by PTTG1. Further evidence suggests that PTTG1IP may have a direct role in cancer. Initially, PTTG1IP expression was found to be higher in pituitary tumours compared with normal pituitary tissue. In particular, PTTG1IP has been shown to regulate thyroid cell growth, with overexpression resulting in

hyperplasia Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of Tissue (biology), organic tissue that results from ...

and the formation of lesions within the thyroid gland. PTTG1IP expression has also been independently associated with tumour recurrence and subcutaneous expression results in tumour formation in nude mice. PTTG1IP is also implicated in breast cancer. Immunohistochemical analysis of tissue samples has revealed that PTTG1IP is strongly expressed in several types and grades of breast cancer. Furthermore, overexpression and secretion of PTTG1IP induces cell invasion, a process that is essential for the formation of metastatic disease. Furthermore, PTTG1IP has been reported to regulate the expression of the human

sodium-iodide symporter The sodium/iodide cotransporter, also known as the sodium/iodide symporter (NIS), is a protein that in humans is encoded by the ''SLC5A5'' gene. It is a transmembrane glycoprotein with a molecular weight of 87 kAtomic mass unit, Da and 13 transmem ...

(NIS). NIS is expressed by thyroid follicular epithelial cells and is responsible for iodine transport and uptake. The ability of the thyroid to accumulate iodine provides the basis for radioiodine ablation of thyroid tumours and their metastases. Overexpression of PTTG1 or PTTG1IP inhibits NIS mRNA expression and iodide uptake in human and rat thyroid cells. This has important implications for radioiodine ablation therapy and highlights PTTG1IP as a novel target for improving radioiodine uptake by thyroid tumours.

Interactions

PTTG1IP has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with: *

PTTG1 Securin is a protein that in humans is encoded by the ''PTTG1'' gene. Function The encoded protein is a homolog of yeast securin proteins, which prevent separins from promoting sister chromatid separation. It is an anaphase-promoting complex ...

, * MCT8, and * NIS.

Structure

Function

Interactions

References

Further reading