DNA-binding protein Ikaros also known as Ikaros family zinc finger protein 1 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 ''IKZF1''

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 ...

Ikaros - transcription factor

Ikaros is a transcription factor that is encoded by the ''IKZF'' genes of the Ikaros family

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 ...

group. Zinc finger is a small structural motif of protein that allows protein binding to DNA or RNA molecule that is characterized by the coordination of one or more zinc ions (Zn²⁺) in order to stabilize the fold. Ikaros displays crucial functions in the

hematopoietic Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...

system and is a known regulator of

immune cells White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

development, mainly in early

B cells 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 ...

CD4+ T cells In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic ce ...

. Its dysfunction has been linked to the development of chronic lymphocytic leukemia. In particular, Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia and that it also has a part in the differentiation and function of individual

T helper The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are consider ...

cells. Ikaros also has a role during the later stages of B cell development during VDJ recombination in switch class of the

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

isotypes and expression of the B cell receptor. In Ikaros knockout mice, T cells but not B cells are generated late in mouse development due to late compensatory expression of the related gene Aiolos (IKZF3). Ikaros point mutant mice are embryonic lethal due to anemia; they have severe defects in terminal

erythrocyte Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

and

granulocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They ha ...

differentiation, and excessive

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

formation. SNPs located near the 3' region of IKZF1 in humans have been linked to susceptibility to childhood acute lymphoblastic leukemia (ALL) as well as

type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...

. The two effects appear to be in opposite directions, with the allele marking susceptibility to

ALL All or ALL may refer to: Language * All, an indefinite pronoun in English * All, one of the English determiners * Allar language (ISO 639-3 code) * Allative case (abbreviated ALL) Music * All (band), an American punk rock band * ''All'' (All al ...

protecting from T1D and vice versa.

Genes of the Ikaros Zinc Finger Family group

The Ikaros Zinc Finger (IkZF) family of

transcription factors In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The func ...

are known regulators of hematopoietic cell development and many immune cells including that of CD4⁺ T cells. The IkZF family consists of five members: Ikaros (encoded by the gene ''Ikzf1''), Helios (''

Ikzf2 Zinc finger protein Helios is a protein that in humans is encoded by the ''IKZF2'' gene. This protein is a member of Ikaros family of transcription factors. This gene encodes a member of the Ikaros family of zinc-finger proteins. This family of t ...

''), Aiolos (''

Ikzf3 Zinc finger protein Aiolos also known as Ikaros family zinc finger protein 3 is a protein that in humans is encoded by the ''IKZF3'' gene. Function This gene encodes a member of the Ikaros family of zinc-finger proteins. Three members of this ...

''), Eos (''

Ikzf4 Zinc finger protein Eos is a protein that in humans is encoded by the ''IKZF4'' gene. Members of the Ikaros (ZNFN1A1; MIM 603023) family of transcription factors, which includes Eos, are expressed in lymphocytes and are implicated in the control o ...

''), and Pegasus ('' Ikzf5''). These factors contain N-terminal zinc finger (ZF) domains, which are responsible for mediating direct interactions with DNA, and C-terminal ZFs, which facilitate homo- and heterodimerization between IkZF family members. IKZF1 is upregulated in granulocytes, B cells, CD4 and CD8 T cells, and NK cells, and downregulated in erythroblasts, megakaryocytes and monocytes.

Ikaros deficiency

The mutation in the ''IKZF1'' gene can cause dysfunction of the Ikaros transcription factor. The dysfunction affects expression in

that can lead to deregulation of the BCR signaling during B cell development and is associated with B cell transformation. The deregulation then can result in low proliferation rate and increased

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

of the B cells. The deregulation may be related with

lymphoproliferative disorders Lymphoproliferative disorders (LPDs) refer to a specific class of diagnoses, comprising a group of several conditions, in which lymphocytes are produced in excessive quantities. These disorders primarily present in patients who have a compromised i ...

and different forms of

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

Interactions

IKZF1 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: *

CTBP1 C-terminal-binding protein 1 also known as CtBP1 is a protein that in humans is encoded by the ''CTBP1'' gene. CtBP1 is one of two CtBP proteins, the other protein being CtBP2. Function The CtBP1 protein was originally identified as a human prote ...

, *

HDAC1 Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the ''HDAC1'' gene. Function Histone acetylation and deacetylation, catalyzed by multisubunit complexes, play a key role in the regulation of eukaryotic gene expression. T ...

, *

HDAC7A Histone deacetylase 7 is an enzyme that in humans is encoded by the ''HDAC7'' gene. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters ...

, *

Histone deacetylase 5 Histone deacetylase 5 is an enzyme that in humans is encoded by the ''HDAC5'' gene. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alter ...

, *

IKZF2 Zinc finger protein Helios is a protein that in humans is encoded by the ''IKZF2'' gene. This protein is a member of Ikaros family of transcription factors. This gene encodes a member of the Ikaros family of zinc-finger proteins. This family of t ...

, *

IKZF3 Zinc finger protein Aiolos also known as Ikaros family zinc finger protein 3 is a protein that in humans is encoded by the ''IKZF3'' gene. Function This gene encodes a member of the Ikaros family of zinc-finger proteins. Three members of this ...

, *

IKZF4 Zinc finger protein Eos is a protein that in humans is encoded by the ''IKZF4'' gene. Members of the Ikaros (ZNFN1A1; MIM 603023) family of transcription factors, which includes Eos, are expressed in lymphocytes and are implicated in the control o ...

, *

SIN3A Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the ''SIN3A'' gene. Function The protein encoded by this gene is a transcriptional regulatory protein. It contains paired amphipathic helix (PAH) domains, which a ...

, * Cereblon *

SIN3B Paired amphipathic helix protein Sin3b is a protein that in humans is encoded by the ''SIN3B'' gene. Interactions SIN3B has been shown to interact with HDAC1, Zinc finger and BTB domain-containing protein 16, SUDS3 and IKZF1. See also * Tra ...

. *

GATA2 GATA2 or GATA-binding factor 2 is a transcription factor, i.e. a nuclear protein which regulates the expression of genes. It regulates many genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of b ...

References

External links