P14arf

p14P14 ARF alternate open reading frame (ARF)ARFINK4/ARF tumor suppressorp19 Arf p19 ARF ''/''p14 ARF p19ARF
p14ARF (also called ARF tumor suppressor, ARF, p14 ARF ) is an alternate reading frame protein product of the CDKN2A locus (i.e. INK4a/ARF locus).wikipedia
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P53

TP53p53 genep53 protein
These interactions allow p14ARF to act as a tumor suppressor by inhibiting ribosome biogenesis or initiating p53-dependent cell cycle arrest and apoptosis, respectively. p14ARF inhibits mdm2, thus promoting p53, which promotes p21 activation, which then binds and inactivates certain cyclin-CDK complexes, which would otherwise promote transcription of genes that would carry the cell through the G 1 /S checkpoint of the cell cycle. Loss of p14ARF by a homozygous mutation in the CDKN2A (INK4A) gene will lead to elevated levels in mdm2 and, therefore, loss of p53 function and cell cycle control.
Oncogenes also stimulate p53 activation, mediated by the protein p14ARF.

Mdm2

E3 Ubiquitin-Protein Ligase Mdm2 (MDM2)Hdm2Mdm-2
It accumulates mainly in the nucleolus where it forms stable complexes with NPM or Mdm2. p14ARF inhibits mdm2, thus promoting p53, which promotes p21 activation, which then binds and inactivates certain cyclin-CDK complexes, which would otherwise promote transcription of genes that would carry the cell through the G 1 /S checkpoint of the cell cycle. Loss of p14ARF by a homozygous mutation in the CDKN2A (INK4A) gene will lead to elevated levels in mdm2 and, therefore, loss of p53 function and cell cycle control.
This loop can be interfered with by kinases and genes like p14arf when p53 activation signals, including DNA damage, are high.

P16

CDKN2Ap16INK4ap16 INK4a
p14ARF (also called ARF tumor suppressor, ARF, p14 ARF ) is an alternate reading frame protein product of the CDKN2A locus (i.e. INK4a/ARF locus).
The remaining transcript includes an alternate exon 1 located 20 kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein that is structurally unrelated to the products of the other variants.

Cell cycle

M phasecell cycle progressioncell-cycle
These interactions allow p14ARF to act as a tumor suppressor by inhibiting ribosome biogenesis or initiating p53-dependent cell cycle arrest and apoptosis, respectively.
The INK4a/ARF family includes p16 INK4a, which binds to CDK4 and arrests the cell cycle in G 1 phase, and p14 ARF which prevents p53 degradation.

Mitogen

mitogenicmitogensmitogenesis
p14ARF is induced in response to elevated mitogenic stimulation, such as aberrant growth signaling from MYC and Ras (protein).

Myc

c-MyccMycc-Myb
p14ARF is induced in response to elevated mitogenic stimulation, such as aberrant growth signaling from MYC and Ras (protein).

Ras GTPase

RasRas subfamilyRas protein
p14ARF is induced in response to elevated mitogenic stimulation, such as aberrant growth signaling from MYC and Ras (protein).

Nucleolus

nucleolinucleolarcell nucleolus
It accumulates mainly in the nucleolus where it forms stable complexes with NPM or Mdm2.

Tumor suppressor

tumor suppressor genetumor suppressor genestumour suppressor gene
These interactions allow p14ARF to act as a tumor suppressor by inhibiting ribosome biogenesis or initiating p53-dependent cell cycle arrest and apoptosis, respectively.

Reading frame

reading framesin framein-frame
p14ARF is an atypical protein, in terms of its transcription, its amino acid composition, and its degradation: it is transcribed in an alternate reading frame of a different protein, it is highly basic, and it is polyubiquinated at the N-terminus.

N-terminus

N-terminalN terminusN-
p14ARF is an atypical protein, in terms of its transcription, its amino acid composition, and its degradation: it is transcribed in an alternate reading frame of a different protein, it is highly basic, and it is polyubiquinated at the N-terminus.

P21

CDKN1Ap21Cip1WAF1
p14ARF inhibits mdm2, thus promoting p53, which promotes p21 activation, which then binds and inactivates certain cyclin-CDK complexes, which would otherwise promote transcription of genes that would carry the cell through the G 1 /S checkpoint of the cell cycle.

Cyclin

cyclinscyclin d1mitotic cyclin
p14ARF inhibits mdm2, thus promoting p53, which promotes p21 activation, which then binds and inactivates certain cyclin-CDK complexes, which would otherwise promote transcription of genes that would carry the cell through the G 1 /S checkpoint of the cell cycle.

Cyclin-dependent kinase

CDKcyclin-dependent kinasescyclin dependent kinase
p14ARF inhibits mdm2, thus promoting p53, which promotes p21 activation, which then binds and inactivates certain cyclin-CDK complexes, which would otherwise promote transcription of genes that would carry the cell through the G 1 /S checkpoint of the cell cycle.

Transcription (biology)

transcriptiontranscribedtranscriptional
p14ARF inhibits mdm2, thus promoting p53, which promotes p21 activation, which then binds and inactivates certain cyclin-CDK complexes, which would otherwise promote transcription of genes that would carry the cell through the G 1 /S checkpoint of the cell cycle.

Cell (biology)

cellcellscellular
p14ARF inhibits mdm2, thus promoting p53, which promotes p21 activation, which then binds and inactivates certain cyclin-CDK complexes, which would otherwise promote transcription of genes that would carry the cell through the G 1 /S checkpoint of the cell cycle.

Cell cycle checkpoint

checkpointcheckpointscell cycle arrest
p14ARF inhibits mdm2, thus promoting p53, which promotes p21 activation, which then binds and inactivates certain cyclin-CDK complexes, which would otherwise promote transcription of genes that would carry the cell through the G 1 /S checkpoint of the cell cycle.

Mutation

mutationsgenetic mutationmutated
Loss of p14ARF by a homozygous mutation in the CDKN2A (INK4A) gene will lead to elevated levels in mdm2 and, therefore, loss of p53 function and cell cycle control.

Protein

proteinsproteinaceousstructural proteins
The p14ARF transcript was first identified in humans in 1995, and its protein product confirmed in mice that same year.

Chromosome 9

9Chromosome 9 (human)9q34
Its gene locus is on the short arm of chromosome 9 in humans, and on a corresponding location on chromosome 4 in mice.

Gene

genesnumber of genesgene sequence
p14ARF inhibits mdm2, thus promoting p53, which promotes p21 activation, which then binds and inactivates certain cyclin-CDK complexes, which would otherwise promote transcription of genes that would carry the cell through the G 1 /S checkpoint of the cell cycle.

Cyclin-dependent kinase 4

CDK44CDK4 gene
These INK4 proteins directly inhibit the cyclin D-dependent kinases CDK4 and CDK6.

Cyclin-dependent kinase 6

CDK66/6
These INK4 proteins directly inhibit the cyclin D-dependent kinases CDK4 and CDK6.

Cancer

cancersmalignanciescancerous
There are other INK4 genes on other chromosomes, however these are not linked to cancer, and so their functions are not likely to be overlapping.

Retinoblastoma protein

RB1RbpRb
An important cyclin-dependent substrate is the retinoblastoma protein Rb, which is phosphorylated in late gap 1 phase (G1 phase), allowing G1 exit.