BMI1 polycomb ring finger oncogene, also known as BMI1, is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 which in humans is encoded by the BMI1 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

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Function

BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) has been reported as an oncogene

Oncogene

An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...

 by regulating p16

P16 (gene)

Cyclin-dependent kinase inhibitor 2A, also known as multiple tumor suppressor 1 , is a tumor suppressor protein, that in humans is encoded by the CDKN2A gene...

 and p19

CDKN2D

Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene.Note, this protein should not be confused with p19-ARF or the human equivalent p14-ARF, which are alternative products of the CDKN2a gene....

, which are cell cycle

Cell cycle

The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...

 inhibitor genes. Bmi1 knockout in mice results in defects in hematopoiesis, skeletal patterning, neurological functions, and development of the cerebellum. Recently it has been reported BMI1 is rapidly recruited to sites of DNA damage and it sustains for over than 8h. Loss of BMI1 leads to radiation sensitive and impaired repair of DNA double-strand breaks by homologous recombination 10.

Bmi1 is necessary for efficient self-renewing cell divisions of adult hematopoietic stem cells as well as adult peripheral and central nervous system neural stem cells. However, it is less important for the generation of differentiated progeny. Given that phenotypic changes in Bmi1 knockout mice are numerous and that Bmi1 has very broad tissue distribution, it is possible that it regulates the self-renewal of other types of somatic stem cells.

Bmi1 is also thought to inhibit ageing in neurons through the suppression of p53

P53

p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...

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Structure

Bmi1 has a RING finger

RING finger domain

In molecular biology, a RING finger domain is a protein structural domain of zinc finger type which contains a Cys3HisCys4 amino acid motif which binds two zinc cations. This protein domain contains from 40 to 60 amino acids...

 at the N-terminus and a central helix-turn-helix

Helix-turn-helix

In proteins, the helix-turn-helix is a major structural motif capable of binding DNA. It is composed of two α helices joined by a short strand of amino acids and is found in many proteins that regulate gene expression...

 domain.

Clinical significance

Bmi1 seems to play an important role in several types of cancer, such as bladder, skin, prostate, breast, ovarian, colorectal as well as hematological malignancies. Its amplification and overexpression is especially pronounced in mantle cell lymphoma

Mantle cell lymphoma

Mantle cell lymphoma is one of the rarest of the non-Hodgkin's lymphomas , comprising about 6% of NHL cases. There are only about 15,000 patients presently in the U.S. While it is difficult to treat and seldom considered cured, investigations into better treatments are actively pursued worldwide...

s.

Interactions

BMI1 has been shown to interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with Zinc finger and BTB domain-containing protein 16

Zinc finger and BTB domain-containing protein 16

Zinc finger and BTB domain-containing protein 16 is a protein that in humans is encoded by the ZBTB16 gene.-Function:This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor that contains nine Kruppel-type zinc finger domains at the...

, PHC2

PHC2

Polyhomeotic-like protein 2 is a protein that in humans is encoded by the PHC2 gene.-Interactions:PHC2 has been shown to interact with MAPKAPK2, PHC1, BMI1 and MCRS1.-Further reading:...

, PHC1

PHC1

Polyhomeotic-like protein 1 is a protein that in humans is encoded by the PHC1 gene.-Interactions:PHC1 has been shown to interact with BMI1 and PHC2.-Further reading:...

 and RING1

RING1

E3 ubiquitin-protein ligase RING1 is an enzyme that in humans is encoded by the RING1 gene.-Interactions:RING1 has been shown to interact with CBX8, BMI1 and RYBP.-Further reading:...

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Further reading