Sinkkisormiproteiinit sairaudessa.Tuumorisuppressorit ja onkogeenifunktiot.

LÄHDE: M.Cassandri (2017): Role of ZNFs in diseases.

• ZNF-proteiinit tuumorisuppressoreina ja onkogeenisinä tekijöinä.

Viime vuosien tutkimukset ovat valaisseet sinkkisormiproteiinien tärkeyttä sekä tuumorisupressorigeeneinä että onkogeeneinä. Sinkkisormiproteiineja (ZNF) on mukana kaikissa  syövän progredioitumisen pääteissä karsinogeneesistä metastaasien muodostukseen asti. Lisäksi ZNF- proteiinit osallistuvat syöpään transkriptiofaktorifunktiollaan. Myös  on saatu kasvavaa näyttöä sinkkisormiproteiinien merkityksestä kromatiinin muovaajien rekrytoijina tai rakenteellisina proteiineina, jotka säätävät syöpäsolun migroitumista ja invasoitumista.
M. Cassandri käsittelee erikseen seuraavat ZNF proteiinit, joista olen ottanut PubMed hakutietoja.

ZNF281 (1q32.1), https://www.ncbi.nlm.nih.gov/gene/23528

Preferred Names: zinc finger protein 281.
Names:
GC-box-binding zinc finger protein 1
ZNP-99 transcription factor
transcription factor ZBP-99
zinc finger DNA-binding protein 99

ZNF750 (17q25.3) , https://www.ncbi.nlm.nih.gov/gene/?term=ZNF750
 This gene encodes a protein with a nuclear localization site and a C2H2 zinc finger domain. Mutations in this gene have been associated with seborrhea-like dermatitis with psoriasiform elements. [provided by RefSeq, Jul 2008]
 

ZNF185, (Xq28), https://www.ncbi.nlm.nih.gov/gene/7739
SCELL. Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This gene encodes a LIM-domain zinc finger protein. The LIM domain is composed of two contiguous zinc finger domains, separated by a two-amino acid residue hydrophobic linker. The LIM domain mediates protein:protein interactions. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, May 2010].

Preferred Names: zinc finger protein 185. 

Names:

 P1-A,

sciellin like,

zinc finger protein 185 (LIM domain). 

ZBP89, ZNF148, (3q21.2 ), https://www.ncbi.nlm.nih.gov/gene/7707 , BERF-1; BFCOL1; GDACCF; ZBP-89; ZFP148; pHZ-52; HT-BETA
The protein encoded by this gene is a member of the Kruppel family of zinc finger DNA binding proteins. The encoded protein activates transcription of the T-cell receptor and intestinal alkaline phosphatase genes but represses transcription of the ornithine decarboxylase, vimentin, gastrin, stomelysin, and enolase genes. Increased expression of this gene results in decreased patient survival rates from colorectal cancer, while mutations in this gene have been associated with global developmental delay, hypoplastic corpus callosum, and dysmorphic facies. [provided by RefSeq, Feb 2017] Preferred Names zinc finger protein 148.

Names:

 CACCC box-binding protein,

CLL-associated antigen KW-10,

transcription factor ZBP-89,

zinc finger DNA-binding protein 89.

MDM2 (12q15) proto-oncogene, https://www.ncbi.nlm.nih.gov/gene/4193
 HDMX, hdm2, ACTFS. Preferred Names:E3 ubiquitin-protein ligase Mdm2
Names: MDM2 oncogene, E3 ubiquitin protein ligase,
MDM2 proto-oncogene, E3 ubiquitin protein ligase,
Mdm2, p53 E3 ubiquitin protein ligase homolog,
Mdm2, transformed 3T3 cell double minute 2, p53 binding protein,
double minute 2, human homolog of; p53-binding protein,
oncoprotein Mdm2.

ZEB1  (10p11.22) https://www.ncbi.nlm.nih.gov/gene/6935
BZP; TCF8; AREB6; FECD6; NIL2A; PPCD3; ZFHEP; ZFHX1A; DELTAEF1. This gene encodes a zinc finger transcription factor. The encoded protein likely plays a role in transcriptional repression of interleukin 2. Mutations in this gene have been associated with posterior polymorphous corneal dystrophy-3 and late-onset Fuchs endothelial corneal dystrophy. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Mar 2010]Preferred Names: zinc finger E-box-binding homeobox 1,
Names: delta-crystallin enhancer binding factor 1,
negative regulator of IL2,
posterior polymorphous corneal dystrophy 3,
transcription factor 8 (represses interleukin 2 expression.


ZNF neurologisissa taudeissa

ZPR1 (11q23.3), https://www.ncbi.nlm.nih.gov/gene/8882
ZNF259. The protein encoded by this gene is found in the cytoplasm of quiescent cells but translocates to the nucleolus in proliferating cells. The encoded protein interacts with survival motor neuron protein (SMN1) to enhance pre-mRNA splicing and to induce neuronal differentiation and axonal growth. Defects in this gene or the SMN1 gene can cause spinal muscular atrophy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015] Preferred Names: zinc finger protein ZPR1

Names: zinc finger protein 259. 

ZNF179, RNF112 (17p11.2),https://www.ncbi.nlm.nih.gov/gene/7732
BFP; ZNF179. This gene encodes a member of the RING finger protein family of transcription factors. The protein is primarily expressed in brain. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]. Preferred Names: RING finger protein 112.
Names: brain finger protein,
neurolastin,
zinc finger protein 179.

ZNF746, PARIS, (7q36.1) (https://www.ncbi.nlm.nih.gov/gene/155061

Preferred Names: zinc finger protein 746.

Names: parkin-interacting substrate,

• ZNFs in other human diseases:

ZNF750 ( lähde  mainittu ylhäällä) .

GLIS1, (1p32.3)  (, https://www.ncbi.nlm.nih.gov/gene/148979
 GLIS1 is a GLI (MIM 165220)-related Kruppel-like zinc finger protein that functions as an activator and repressor of transcription (Kim et al., 2002 [PubMed 12042312]).[supplied by OMIM, Mar 2008] Expression: Low expression observed in reference dataset.

Preferred Names: zinc finger protein GLIS1.

Names: GLI-similar 1.

GLIS3, (9p24.2)  https://www.ncbi.nlm.nih.gov/gene/169792.
NDH; ZNF515. This gene is a member of the GLI-similar zinc finger protein family and encodes a nuclear protein with five C2H2-type zinc finger domains. This protein functions as both a repressor and activator of transcription and is specifically involved in the development of pancreatic beta cells, the thyroid, eye, liver and kidney. Mutations in this gene have been associated with neonatal diabetes and congenital hypothyroidism (NDH). Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only two have been determined. [provided by RefSeq, Jul 2008]

Preferred Names: zinc finger protein GLIS3.

Names: GLI-similar 3.

OK/KNS-cl.4,

.zinc finger protein 515

GATA-4, (8p23.1), https://www.ncbi.nlm.nih.gov/gene/2626
TOF; ASD2; VSD1; TACHD This gene encodes a member of the GATA family of zinc-finger transcription factors. Members of this family recognize the GATA motif which is present in the promoters of many genes. This protein is thought to regulate genes involved in embryogenesis and in myocardial differentiation and function, and is necessary for normal testicular development. Mutations in this gene have been associated with cardiac septal defects. Additionally, alterations in gene expression have been associated with several cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015].

Preferred Names: transcription factor GATA-4. Names: GATA-binding factor 4.

GATA-6, (18q11.2)  https://www.ncbi.nlm.nih.gov/gene/2627.
This gene is a member of a small family of zinc finger transcription factors that play an important role in the regulation of cellular differentiation and organogenesis during vertebrate development. This gene is expressed during early embryogenesis and localizes to endo- and mesodermally derived cells during later embryogenesis and thereby plays an important role in gut, lung, and heart development. Mutations in this gene are associated with several congenital defects. [provided by RefSeq, Mar 2012.

Preferred Names: transcription factor GATA-6. Names: GATA-binding factor 6: