B-cell lymphoma/leukemia 11B 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 in humans is encoded by the ''BCL11B''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Gene location

BCL11B is located on

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

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+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...

protein and is closely related to

BCL11A B-cell lymphoma/leukemia 11A is a protein that in humans is encoded by the ''BCL11A'' gene. Function The ''BCL11A'' gene encodes for a regulatory C2H2 type zinc-finger protein, that can bind to the DNA. Five alternatively spliced transcript va ...

, 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 d ...

(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 other animals, including some species of fish. It makes up the normally visible part of the tooth, covering the Crown (tooth), crown. The ...

) 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 using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

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 hormone receptor family of steroid horm ...

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 A T cell is a type of lymphocyte. T cells are one of the important white blood cells 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 rec ...

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

B cell B cells, also known as B lymphocytes, are a type of white blood cell 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 ...

s and

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

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, mi ...

- 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 desc ...

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 (''cranio-'' combining form meaning head or skull + ''-facial'' combining form referring to the facial structures grossly) is an adjective referring to the parts of the head enclosing the brain and the face. The term is typically used ...

dimorphism, different types of

dermatitis Dermatitis is inflammation of the skin, 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. The area of skin involved can v ...

. As well the

intellectual An intellectual is a person who engages in critical thinking, research, and reflection about the reality of society, and who proposes solutions for the normative problems of society. Coming from the world of culture, either as a creator or a ...

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 of a patient and to produc ...

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 t ...

mode of

inheritance Inheritance is the practice of receiving private property, Title (property), titles, debts, entitlements, Privilege (law), privileges, rights, and Law of obligations, obligations upon the death of an individual. The rules of inheritance differ ...

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. Mo ...

in the BCL11B

Research projects

mouse model A model organism (often shortened to model) 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 working ...

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

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

. Bcl11b gene knock-out in certain

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells 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 r ...

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 in 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 deri ...

and changes in

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

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 reg ...

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 GI tract contains all the major organs of the digestive system, in humans ...

. 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). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...

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 protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

, a well-known

tumor suppressor gene A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a 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 in a loss or red ...

References

External links

* * * * Transcription factors {{gene-14-stub