Genes ink4. Medical search. Frequent questions

Enforced expression of INK4 proteins can lead to G1 arrest by promoting redistribution of Cip/Kip proteins and blocking cyclin E-CDK2 activity. (wikipedia.org)
In addition, INK4 proteins play roles in cellular senescence, apoptosis and DNA repair. (wikipedia.org)
INK4 proteins are tumor suppressors and loss-of-function mutations lead to carcinogenesis. (wikipedia.org)
INK4 proteins are highly similar in terms of structure and function, with up to 85% amino acid similarity. (wikipedia.org)
Polymorphisms of the p15INK4b/p16INK4a homolog were found to segregate with melanoma susceptibility in the Xiphophorus indicating that INK4 proteins have been involved with tumor suppression for over 350 million years. (wikipedia.org)
INK4 proteins are cell-cycle inhibitors. (wikipedia.org)
Cells containing oncogenic mutations in-vivo often responded by activating the INK4A/ARF/INK4B locus that encodes the INK4 tumor suppressor proteins. (wikipedia.org)
The CDKN2A gene provides instructions for making several proteins. (medlineplus.gov)
Our results suggest that in young cells Polycomb proteins are recruited to the INK4/ARF locus through CDC6 and the resulting silent locus is replicated during late S-phase. (plos.org)
Mole rat biology is a bit smarter than that-while they do experience cellular senescence, thanks to a handful of proteins synthesized by their genes, it's more controlled. (wired.me)
Similar to humans and mice, mole rats have a cluster of genes (a gene locus named INK4) that allows the body to create cancer-fighting proteins. (wired.me)
While these genes encode three proteins in humans and mice, mole rats can synthesize a fourth cancer-fighting protein, which is even better than its counterparts at stopping cell division. (wired.me)
Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (thermofisher.com)
p18INK4C is a member of the INK4 family of proteins that regulate the G1 to S cell cycle transition by binding to and inhibiting the pRb kinase activity of cyclin-dependent kinases 4 and 6 (1). (rockland.com)
This domain occurred 402 times on human genes ( 935 proteins). (umbc.edu)
Two genes encoding putative internalin proteins were chosen for further study. (omictools.com)

INK4 is a family of cyclin-dependent kinase inhibitors (CKIs). (wikipedia.org)
Various techniques have been developed for targeting cancer cells: gene therapy, monoclonal antibodies (MAbs), antibody toxin conjugates, small-molecule inhibitors, antisense molecules, and tumor vaccines. (medscape.com)
The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. (cancerindex.org)
Upstream inhibitors, including members of the Ink4 and Cip/Kip families, inhibit the mitogenic action of CDKs. (shu.edu)
On the other hand, for the immune checkpoint inhibitors, such as anti-PD-1 antibodies (nivolumab and pembrolizumab) and anti-PD-L1 antibodies (atezolizumab and durvalumab), as well as molecular targeted drugs for various driver gene mutations, there is little data at the time of publication of the statement and no categorization by risk. (encyclopedia.pub)
p15INK4B is a member of your INK4 family members of CDK inhibitors, which binds to CDK4 and CDK6 subunits, inactivates their catalytic ac tivity and prevents cyclin D CDK4 six complex formation. (mirnaarray.com)
They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. (umbc.edu)

The INK4a/ARF/INK4b locus encodes three genes (p15INK4b, ARF, and p16INK4a) in a 35-kilobase stretch of the human genome. (wikipedia.org)
This observation yields two possible opposing conclusions: Either tumor formation does not provide any evolutionary selection pressure because the overlapping INK4a/ARF/INK4b is not selected against or tumorigenesis provides such a strong pressure, that an entire group of genes has been selected for at the INK4a/ARF/INK4b locus to prevent cancer. (wikipedia.org)
A different type of alteration involving the CDKN2A gene can result in reduced amounts or an absence of the p16(INK4A) or p14(ARF) protein. (medlineplus.gov)
The CDKN2A gene mutations found in melanoma result in a nonfunctional p16(INK4A) protein. (medlineplus.gov)
CDKN2A gene mutations involved in cancer impair production of functional p16(INK4A) or, less commonly, p14(ARF), which can result in uncontrolled cell growth and tumor formation. (medlineplus.gov)
also known as CDK4I, Cyclin-dependent kinase 4 inhibitor A, Multiple tumor suppressor 1, MTS-1, p16-INK4, p16-INK4a, p16INK4A) is encoded by the CDKN2A (also known as CDKN2, MTS1) gene (Gene ID 1029) in human. (sigmaaldrich.com)
INK4a and INK4b (encoded by the CDKN2A and CDKN2B gene, respectively) constitute the INK4 subfamily of CDKis. (sigmaaldrich.com)
The INK4/ARF locus encodes three tumor suppressor genes (p15 Ink4b , Arf and p16 Ink4a ) and is frequently inactivated in a large number of human cancers. (plos.org)
This loss is accompanied with an increased expression of the histone demethylase Jmjd3 and with the recruitment of the MLL1 protein, and correlates with the expression of the Ink4a/Arf genes. (plos.org)

Mutations in the CDKN2A gene are found in up to one-quarter of head and neck squamous cell carcinomas (HNSCC). (medlineplus.gov)
Mutations in the CDKN2A gene are also associated with melanoma, a type of skin cancer that begins in pigment-producing cells called melanocytes. (medlineplus.gov)
CDKN2A gene mutations are found in up to 40 percent of familial cases of melanoma, in which multiple family members develop the cancer. (medlineplus.gov)
In about half of melanomas, part or all of the CDKN2A gene is missing (deleted). (medlineplus.gov)
In many other cases, the CDKN2A gene has a mutation or is turned off (inactive). (medlineplus.gov)
Individuals with a CDKN2A gene mutation tend to develop melanoma at an earlier age than those without a mutation in the gene. (medlineplus.gov)
Germline mutations affecting the CDKN2A gene are associated with other cancers, including breast cancer and pancreatic cancer. (medlineplus.gov)
In some families, CDKN2A gene mutations are associated with development of only one type of cancer. (medlineplus.gov)
Gene CDKN2A had been KO in hela cell line. (rc-crispr.com)
The gene view histogram is a graphical view of mutations across CDKN2A_ENST00000530628. (sanger.ac.uk)
Mouse insertional mutagenesis experiments DO NOT support the designation of CDKN2A_ENST00000530628 as a cancer causing gene. (sanger.ac.uk)

Somatic mutations in other genes involved in cell growth are also needed for a melanoma to develop. (medlineplus.gov)
DUSP4 alterations lead to hyperactivation of MAPK signaling in many cancers, including breast cancer, which often harbor mutations in cell cycle checkpoint genes, particularly in TP53. (biomedcentral.com)
These mutations are displayed at the amino acid level across the full length of the gene by default. (sanger.ac.uk)
Considering how mutations in the INK4 gene are linked to human cancers," Gorbunova adds, "the better we understand that gene and control its mutations, the better our chances of controlling some cancers. (wired.me)

This task can be accomplished by replacing tumor suppressor genes that have been lost or mutated, selectively inserting genes that produce cytotoxic substances, or modifying the immune system to destroy the tumor cells. (medscape.com)
Here we show that the Wnt-effector Tcf1 is recruited to and triggers transcription of the Ink4/Arf tumor suppressor locus. (upf.edu)
INK4 locus is located on human chromosome 9p21 region and encodes three tumor suppressor genes, p15, p16 and ARF. (esmo.org)
This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. (rc-crispr.com)
p18INK4C can function as a tumor suppressor gene in Hodgkins lymphoma and its inactivation may contribute to the cell cycle deregulation and defective terminal differentiation characteristic of the Reed-Sternberg cells (2). (rockland.com)

Tcf1, but not Tcf3, is recruited to a palindromic motif enriched in the promoter of cell cycle repressor genes, such as p15Ink4b, p16Ink4a and p19Arf, which mediate the Wnt-dependent anti-proliferative effect in mESCs. (upf.edu)

In this study, we showed that LION is involved in the transcriptional regulation of INK4 locus and cell proliferation. (esmo.org)
To date, it is well known that lncRNAs participate in chromatin modifications and transcriptional and translational regulation of protein-encoding genes or regulate protein function and activity through specific binding [ 3 - 5 ]. (jcancer.org)
In the nucleus, R-SMAD-SMAD4 complexes cooperate with transcriptional coregulators that further define target gene recognition and transcriptional regulation. (shu.edu)
Transcriptional regulation of INK4/ARF locus by cis and trans mechanisms. (ncbs.res.in)
2020. Ligand dependent gene regulation by transient ERα clustered enhancers. . (ncbs.res.in)
The accessibility and transcription of ribosomal genes is controlled at several levels, with their epigenetic regulation being one of the most important. (oncotarget.com)
Genome-wide transcript analysis showed that B. anthracis undergoes considerable changes in gene expression during growth in iron-depleted media, including the regulation of known and candidate virulence factors. (omictools.com)

Low levels of c Myc make it possible for for TGF B induced tran scription of p15INK4B and p21CIP1 genes. (mirnaarray.com)

ANRIL associates with polycomb protein complexes and recruits them on INK4 locus, leading to the transcriptional repression. (esmo.org)
Q-RT-PCR analysis showed that silencing LION increases the p15 and p16 mRNA, suggesting that LION is involved in the transcriptional repression of INK4 locus. (esmo.org)
The phosphorylation of pRB, and relief of transcriptional repression by pRB induces genes involved in the induction of S-phase entry. (shu.edu)

Pieces of information from other database were extracted and added to the extracted gene such as alias name, summary of gene function, gene ontology, SNPs. (urogene.org)

Altered expression of this gene has been observed in multiple human cancers. (cancerindex.org)

BCLC9-miR122 cells down-regulate expression of MYC, KLF4, FOXM1, AKT2 and AKT3 genes and up-regulate FOXO1 and FOXO3A gene expression. (oncotarget.com)
Activated complexes accumulate in the nucleus where they cooperate with DNA-binding cofactors to regulate target gene transcription. (shu.edu)

CVT-313 treatment reduced cdk2-mediated phosphorylation of the retinoblastoma gene product (Rb) on T821, but did not affect cyclin D-cdk4/6-mediated Rb phosphorylation on S807/811. (omecamtivmecarbilactivator.com)
Subsequently, T cells receiving PD-1 signals displayed impaired Cdk2 activation and failed to phosphorylate two critical Cdk2 substrates, the retinoblastoma gene product (Rb) and the TGFβ-specific transcription factor Smad3 , leading to suppression of E2F target genes but enhanced Smad3 transactivation (Figure 3). (shu.edu)
This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (thermofisher.com)

Upon senescence, Jmjd3 is overexpressed and the MLL1 protein is recruited to the locus provoking the dissociation of Polycomb from the INK4/ARF locus, its transcriptional activation and its replication during early S-phase. (plos.org)
Interestingly, replication stress in Brca2-null cells activates p53 and the expression of its target genes, including senescence-inducing Ink4/Arf. (biomedcentral.com)
From 2000 to 2003 he worked with David Beach at the Wolfson Institute for Biomedical Research, University College London, where he screened for genes bypassing senescence, identifying CBX7. (longevity.international)
Although senescent cells repress proliferation-promoting genes, they also induce the gene program necessary for the implementation of senescence. (rupress.org)

Here we show that in young proliferating embryonic fibroblasts (MEFs) the Polycomb Repressive Complex 2 (PRC2) member EZH2 together with PRC1 members BMI1 and M33 are strongly expressed and localized at the INK4/ARF regulatory domain (RD) identified as a DNA replication origin. (plos.org)
These models have proven to be useful to define specific as well as redundant roles among members of these cell cycle regulatory gene families. (nih.gov)
In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. (rc-crispr.com)
Notably, circRNAs display cell-type, tissue-type and developmental-stage specific expression patterns in eukaryotic transcriptome, which reveals their significant regulatory functions in gene expression. (ijbs.com)

So far, we revealed that a long non-coding RNA (lncRNA), ANRIL, transcribed from INK4 locus represses the transcription of p15 and p16 genes. (esmo.org)

The expression of further E2F target genes, as cyclin A, facilitates progression through S phase. (shu.edu)

The genes encoding cdks involved in G1-S progression are often amplified in B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL). (omecamtivmecarbilactivator.com)

The Cyclin D-Cdk4,6/INK4/Rb/E2F pathway plays a key role in controlling cell growth by integrating multiple mitogenic and antimitogenic stimuli. (nih.gov)
The components of this pathway are gene families with a high level of structural and functional redundancy and are expressed in an overlapping fashion in most tissues and cell types. (nih.gov)
Using classical transgenic technology as well as gene-targeting in ES cells, a series of mouse models have been developed to study the in vivo function of individual components of this pathway in both normal homeostasis and tumor development. (nih.gov)
Currently, there are 40 genes in SZGR 2.0 (with evidence in schizophrenia) that are present at this pathway. (uth.edu)

Together, these results provide a unified model that integrates replication, transcription and epigenetics at the INK4/ARF locus. (plos.org)

MicroRNAs (miRs) are regulators of gene expression by destabilizing and inducing degradation of messenger RNAs (mRNA) and/or repressing their translation [ 1 ]. (oncotarget.com)
More importantly, circRNAs serve as microRNA (miRNA) sponges and crucial regulators of gene expression. (ijbs.com)

A total of 330 significantly differential genes were identified through large-scale transcriptome sequencing, among which 103 genes were upregulated and 227 genes were downregulated. (mdpi.com)

The goal of gene therapy is to introduce new genetic material into cancer cells that selectively kills them without causing toxicity to the surrounding cells. (medscape.com)
Data extraction: MEDLINE abstracts from each query were carefully read by two scientists to identify true relationship between a gene and the prostate and to extract gene name, type of molecular and genetic events, type of prostatic diseases. (urogene.org)
Larger studies are required to confirm our findings and to elucidate mechanisms by which the genetic interaction between these two genes influences healthspan in pediatric NAFLD. (ljmu.ac.uk)

Mechanisms regulating INK4/ARF expression are not fully characterized. (plos.org)

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue. (lookformedical.com)

1 The CKS1B gene, located at 1q21.3, has been shown to become both duplicated and rearranged over the course of MM progression. (empiregenomics.com)
Genes necessary for cell cycle progression, such as E2F-dependent genes, are incorporated into the SAHF and are thereby silenced, contributing to the stability of the growth arrest. (rupress.org)

This allows the hypophosphorylated Rb to repress transcription of S-phase genes causing cell cycle arrest in the G1 phase. (wikipedia.org)
We found that Dusp4 loss alone is insufficient in mediating tumorigenesis, but alternatively converges with loss in Trp53 and MYC amplification to induce tumorigenesis primarily through chromosome 5 amplification, which specifically upregulates Dbf4 , a cell cycle gene that promotes cellular replication by mediating cell cycle checkpoint escape. (biomedcentral.com)
P15 INK4 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclind-CDK4,6, inhibiting it from hypophosphorylating Rb, thereby, rendering the cell cycle unresponsive to external proliferation signals. (shu.edu)

In many cases, a second, somatic mutation occurs in the normal copy of the gene in melanocytes. (medlineplus.gov)
A mutation in this gene resulting in reduced cell proliferation, and impaired cell motility and polarity, and has been identified in patients with primary microcephaly. (cancerindex.org)

INK4 is the most commonly mutated gene locus in the human cancer," says Professor Andrei Seluanov, part of University of Rochester team of researchers. (wired.me)
For example, a typical question scientists may ask when searching MEDLINE database is: What genes have been found mutated in human prostate cancer? (urogene.org)
Studies of human genome demonstrate that protein-coding genes only occupy less than 2% of the entire genome [ 1 ]. (ijbs.com)

When they bind to CDK4 and CDK6, they induce an allosteric change that leads to the formation of CDK-INK4 complexes rather than CDK-cyclin complexes. (wikipedia.org)

ncRNAs play important roles in controlling gene expression at both transcriptional and post-transcriptional levels. (ijbs.com)

Other INK4 family members did not affect this process. (wikipedia.org)
The INK4 family has been implicated in the aging process. (wikipedia.org)
The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. (cancerindex.org)
JmjC domain-containing histone demethylase 1B (JHDM1B, also called FBXL10 or KDM2B) is a conserved and ubiquitously expressed member of the JmjC domain-containing histone demethylase (JHDM) family involved in the demethylation of trimethylated lysine 4 on histone H3 (H3K4me3) and dimethylated lysine 36 on histone H3 (H3K36me2), thereby removing active chromatin marks and inhibiting gene transcription [ 2 - 4 ]. (oncotarget.com)

Search results: The pahtway p623 has 54 genes in the original annotation. (uth.edu)

Recent progress over the last two decades in the field of molecular genetics, especially with new tools such as genome-wide association studies, has helped to identify new genes and their variants, which can be used for calculations of risk, prediction of treatment efficacy, or detection of subjects prone to drug side effects. (mdpi.com)
Summary: Comparative genomics remains a pivotal strategy to study the evolution of gene organization, and this primacy is reinforced by the growing number of full genome sequences available in public repositories. (omictools.com)

In these cellular models, prolonged JHDM1B downregulation triggered a surge of 45S pre-rRNA transcription and processing, associated with a re-modulation of the H3K36me2 levels at rDNA loci and with changes in DNA methylation of specific CpG sites in rDNA genes. (oncotarget.com)

Furthermore, the older INK4-based system has been further bolstered by the evolution of the recent addition of the ARF-based anti-cancer response. (wikipedia.org)
LION is involved in the promotion of cancer cells proliferation such as H1299 and HCT116 cells via regulating p15, p16 and other genes related to G2/M phase control. (esmo.org)
This is NOT a known cancer gene. (sanger.ac.uk)
It is not found in the Cancer Gene Census . (sanger.ac.uk)
This gene does not have a cancer hallmark. (sanger.ac.uk)
The researchers call this "more systematic changes in their genes", balancing cancer resistance and anti-aging. (wired.me)
The extra protein in mole rats responds to high-cell density, in the presence of high molecular weight hyaluronic acid (HMW-HA), triggering the anti-cancer response of the INK4 gene. (wired.me)
Mice with this version of the gene were better protected against spontaneous tumors and chemically induced skin cancer, had improved health and lived longer than other mice. (wired.me)
Modern approaches to treating cancer take advantage of critical biochemical differences between cancer cells and normal cells - from radiation therapy to chemotherapy to experimental gene therapy. (janechin.net)

Targeted molecular therapy, like therapy with monoclonal antibodies, gene therapy, and other therapies, has limited or nonexistent side effects on normal cells of the body, unlike present modalities such as surgery, chemotherapy, and radiotherapy. (medscape.com)
The first category is genes that have been documented in literature to be involved in the following molecular events in normal prostate or diseased prostate. (urogene.org)

Subsequently released E2F factors mediate expression of pro-proliferative genes including cyclin E and Cdc25A. (shu.edu)

When that gene is deleted or silenced, it often results in the formation of tumors. (wired.me)

Thus, the loss of fine-tuning of gene expression in ageing tissues and the resulting failure to respond appropriately to intrinsic and extrinsic cellular stressors has the potential to be a major contributor to the increased physiological frailty seen in aging organisms [ 8 ]. (beds.ac.uk)

This gene generates several transcript variants which differ in their first exons. (rc-crispr.com)

It has been known for many years that the fundamental transforming event in BL is the translocation of the MYC gene, and the events that bring about this translocation and those that allow cells to survive with the constitutive expression of MYC have been the subject of intense investigation. (bmj.com)

Anatomy7

Organisms6

Diseases8

Chemicals and Drugs38

Analytical, Diagnostic and Therapeutic Techniques and Equipment5

Psychiatry and Psychology1

Phenomena and Processes25

Disciplines and Occupations1

Technology, Industry, Agriculture1

Information Science3

Proteins16

Inhibitors7

INK4a9

CDKN2A11

Mutations4

Tumor suppressor5

P16INK4a1

Regulation7

P15INK4b1

Repression3

Ontology1

Cancers1

Regulate2

Retinoblastoma3

Senescence4

Regulatory4

ANRIL1

Target genes1

CDKs1

Pathway4

Epigenetics1

Regulators of gene expression2

Transcriptome1

Genetic3

Mechanisms1

Differential1

Progression2

Cell cycle3

Mutation2

Human3

Induce1

Roles1

Family4

Annotation1

Genome2

Methylation1

Cancer9

Molecular2

Mediate1

Tumors1

Cellular1

Variants1

Cells1