B-cell lymphoma/leukemia 11B is a

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 ''BCL11B''

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 ...

Gene location

BCL11B is located on

human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...

14p32.2. The

mouse A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus'' ...

analogue is called Rit1 or Bcl11b and is located on

12.

Function

This gene encodes a C2H2-type

zinc finger A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) which stabilizes the fold. The term ''zinc finger'' was originally coined to describe the finger-like appearance of a ...

protein and is closely related to BCL11A, a gene whose translocation may be associated with B-cell malignancies. The specific function of this gene has not yet been determined, but it could also be involved in some malignancies. Two alternatively spliced transcript variants, which encode distinct isoforms, have been reported. Research suggests that BCL11B is crucial for

ameloblasts Ameloblasts are cells present only during tooth development that deposit tooth enamel, which is the hard outermost layer of the tooth forming the surface of the crown. Structure Each ameloblast is a columnar cell approximately 4 micrometers in ...

(the cells that produce

tooth enamel Tooth enamel is one of the four major Tissue (biology), tissues that make up the tooth in humans and many animals, including some species of fish. It makes up the normally visible part of the tooth, covering the Crown (tooth), crown. The other ...

) to form and work properly.*

Interactions

BCL11B 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

COUP-TFI COUP-TF1 (COUP Transcription Factor 1) also known as NR2F1 (Nuclear Receptor subfamily 2, group F, member 1) is a protein that in humans is encoded by the ''NR2F1'' gene. This protein is a member of nuclear receptor, nuclear hormone receptor fami ...

Pathology

BCL11B is closely connected with immune regulation and for so its mutation can lead to a SCID phenotype. This so-called Immunodeficiency 49
OMIM #617237
is classified as T-B+NK+ SCID. It is characterised by a lack of

T lymphocytes T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes A lymphocyte is a type of white blood cell (leukoc ...

and its malfunctioning specifically in proliferative response. On the other hand,

B cell B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...

s and

NK cells Natural killer cells, also known as NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system. They are a kind of large granular lymphocytes (LGL), and belong to the rapidly expanding family of known innate lymphoid cell ...

counts and functions are not impaired. The symptoms of SCID caused by BCL11B

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

- apart from

immunity Immunity may refer to: Medicine * Immunity (medical), resistance of an organism to infection or disease * ''Immunity'' (journal), a scientific journal published by Cell Press Biology * Immune system Engineering * Radiofrequence immunity ...

defects - typically include

teeth A tooth (: teeth) is a hard, calcified structure found in the jaws (or mouths) of many vertebrates and used to break down food. Some animals, particularly carnivores and omnivores, also use teeth to help with capturing or wounding prey, tear ...

abnormalities,

craniofacial Craniofacial surgery is a surgical subspecialty that deals with congenital and acquired deformities of the head, skull, face, neck, jaws and associated structures. Although craniofacial treatment often involves manipulation of bone, craniofacial ...

dimorphism, different types of

dermatitis Dermatitis is a term used for different types of skin inflammation, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened ...

. As well the

intellectual An intellectual is a person who engages in critical thinking, research, and Human self-reflection, reflection about the nature of reality, especially the nature of society and proposed solutions for its normative problems. Coming from the wor ...

development is significantly impaired. The disease has a very early onset and the only known treatment is

hematopoietic stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce ...

from a healthy donor. The immunodeficiency has a

dominant negative In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...

mode of

inheritance Inheritance is the practice of receiving private property, titles, debts, entitlements, privileges, rights, and obligations upon the death of an individual. The rules of inheritance differ among societies and have changed over time. Offi ...

as all so far described patients with it has been after

sequencing In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which succ ...

identified as

heterozygotes Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

in the BCL11B

Research projects

mouse model A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Mod ...

based study showed, that Bcl11b also plays an important role in pathogenesis of

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...

. Bcl11b gene knock-out in certain

T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

population led to development of IBD. The mechanisms behind are supposed to be reduced suppressor activity of

T regulatory cells T, or t, is the twentieth letter of the Latin alphabet, used in the modern English alphabet, the alphabets of other western European languages and others worldwide. Its name in English is ''tee'' (pronounced ), plural ''tees''. It is d ...

and changes in

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

environment. Bcl11b is suspected to interact with

Foxp3 FOXP3 (forkhead box P3), also known as scurfin, is a protein involved in immune system responses. A member of the FOX protein family, FOXP3 appears to function as a master regulator of the regulatory pathway in the development and function of r ...

and IL10 gene promoters and thus impair its suppressive function in the

intestines The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. ...

. Bcl11b (

analogue of

BCL11B) has been proven to contribute to malignant growth for example in case of

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...

s. That is suspected to be caused by interaction with

p53 p53, also known as tumor protein p53, 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 thou ...

, a well-known

tumor suppressor gene A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell (biology), cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results ...

References

External links

* * * * {{Transcription factors, g2 Transcription factors