Download Gene Section PPP2R4 (protein phosphatase 2A activator, regulatory subunit 4)

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PPP2R4 (protein phosphatase 2A activator,
regulatory subunit 4)
Veerle Janssens
Protein Phosphorylation and Proteomics Group, Department of Molecular Cell Biology, Faculty of
Medicine, University of Leuven, Campus GHB O&N1, Herestraat 49, box 901, B-3000 Leuven, Belgium
(VJ)
Published in Atlas Database: February 2009
Online updated version: http://AtlasGeneticsOncology.org/Genes/PPP2R4ID41817ch9q34.html
DOI: 10.4267/2042/44661
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
(dolichyl pyrophosphate phosphatase 1), CRAT
(carnitine acetyltransferase), PPP2R4,
IER5L (immediate early response 5-like), C9orf106.
Note
In fact the gene name would be better: 'protein
phosphatase 2A, regulatory subunit 4' or 'protein
phosphatase 2A activator', and not a mixture of the two.
Other names: MGC2184; OTTHUMP00000022333;
PP2A; PR53; PTPA
HGNC (Hugo): PPP2R4
Location: 9q34.11
Local order: From centromere to telomere: DOLPP1
DNA/RNA
Figure 1. Schematic representation of PPP2R4 splice variants
The top line represents the PPP2R4 gene. Exons are boxed (5' and 3' UTR are speckled). Introns and the 3' UTR are not drawn to scale.
PTPA alpha and beta are the major transcripts/proteins; PTPA gamma, zeta and eta do not encode functional proteins and probably
result from splicing errors. Gene promoter has been analyzed and resides in a non-methylated CpG island. No TATA or CAAT box. Two
functional yin-yang-1 (YY1) binding sites direct basal promoter expression. Tumor suppressor p53 represses transcription through a
mechanism involving YY1 inhibition
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(1)
48
PPP2R4 (protein phosphatase 2A activator, regulatory subunit 4)
Janssens V
Figure 2. Schematic structure of the PPP2R4 promoter
Two YY1 sites are required for basal PPP2R4 promoter activity and reside within the minimal promoter (nt -67/+38 relative to the start of
transcription which is at +1). Upstream of this minimal promoter a GC-rich Sp1-cluster is present (nt -670/-470) of which the functionality
has not yet been proven. The PPP2R4 promoter resides within an unmethylated CpG island.
Description
Function
The gene encompasses around 40 kb; 11 exons.
Stimulates the phosphotyrosyl phosphatase activity
of the PP2A core heterodimer in the presence of
ATP/Mg2+ (in vitro).
Reactivates the phosphoserine/threonine phospha-tase
activity of an inactive PP2A form in the presence of
ATP/Mg2+. This inactive PP2A is associated with the
PP2A methylesterase (PME-1).
peptidyl
prolyl
cis/trans
ATP/Mg2+-dependent
isomerase acting on Pro190 in the PP2A catalytic
subunit.
Binds to the PP2A heterodimeric core enzyme (A and
C subunit).
Required for the biogenesis of active PP2A.
Reported to be pro- as well as anti-apoptotic.
In Saccharomyces cerevisiae: two orthologues found.
Involved in protection against oxidative damage, G1
progression, G2/M transition, Target of Rapamycin
(TOR) pathway.
Transcription
Several transcripts have been identified, resulting from
alternative splicing; two transcripts in Northern blot of
human placental RNA with probe encompassing exons
1-10: 4.1 kb and 2.8 kb (likely resulting from the use of
different polyadenylation signals).
Alpha isoform: encompasses exons 1,2,3,5-11.
Beta isoform: encompasses exons 1-11.
Gamma isoform: encompasses exons 1,3-11.
Delta isoform: encompasses exons 1,2,5-11.
Epsilon isoform: encompasses exons 1,2,3,6-11.
Zeta isoform: encompasses exons 1,3,5-11.
Eta isoform: encompasses exons 1,5-11.
Alpha, beta, delta, epsilon isoforms can be trans-lated
into functional proteins in vitro; gamma, zeta, eta, are
probably the result of splicing errors.
Pseudogene
None has been described.
Protein
Description
Two isoforms detectable in Western blot of human
placenta and several human cell lines: PTPA alpha, 323
amino acids, 36.8 kDa; PTPA beta, 358 amino acids,
40.7 kDa. pI around 5.8; trypsin-resistant.
Expression
Both isoforms are widely expressed. In a given cell
line, PTPA alpha is about 10x more abundant than
PTPA beta. Very high expression in p53-negative cell
lines (for instance the osteosarcoma cell line Saos-2).
Localisation
Predominantly cytoplasmic.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(1)
Figure 3. PTPA protein structurePTPA is an all alpha-helical
polypeptide, organized into two domains separated by a
groove. Here the ribbon structure of human PTPA is displayed
(derived from PDB code: 2IXM, Leulliot et al., 2006).
49
PPP2R4 (protein phosphatase 2A activator, regulatory subunit 4)
Janssens V
homologues
from
Drosophila
melanogaster
Saccharomyces
cerevisiae. Biochemistry.
1998
15;37(37):12899-908
Homology
No other human homologues known. Defines a new
family of peptidyl prolyl cis/trans isomerases (PPIases)
with all alpha-helical structure, organized into two
domains separated by a groove.
and
Sep
Janssens V, Van Hoof C, De Baere I, Merlevede W, Goris J.
Functional analysis of the promoter region of the human
phosphotyrosine phosphatase activator gene: Yin Yang 1 is
essential for core promoter activity. Biochem J. 1999 Dec
15;344 Pt 3:755-63
To be noted
Janssens V, Van Hoof C, De Baere I, Merlevede W, Goris J.
The phosphotyrosyl phosphatase activator gene is a novel p53
target gene. J Biol Chem. 2000 Jul 7;275(27):20488-95
Note
Although there is a huge and accumulating literature
implicating PP2A in cancer etiology, PP2A enzymes
represent a large and diverse family of holoenzymes,
and the functional implications of specific complexes
are only beginning to emerge. As such, it is clear that
some PP2A holoenzymes may act as tumor
suppressors, whereas others may on the contrary rather
promote tumorigenesis.
As for PPP2R4, one of the many cellular
regulators/subunits of PP2A, there is as yet no direct
evidence that this gene product is directly involved in
these pathological processes.
Janssens V, van Hoof C, Martens E, de Baere I, Merlevede W,
Goris J. Identification and characterization of alternative splice
products encoded by the human phosphotyrosyl phosphatase
activator gene. Eur J Biochem. 2000 Jul;267(14):4406-13
Rempola B, Kaniak A, Migdalski A, Rytka J, Slonimski PP, di
Rago JP. Functional analysis of RRD1 (YIL153w) and RRD2
(YPL152w), which encode two putative activators of the
phosphotyrosyl
phosphatase
activity
of
PP2A
in
Saccharomyces cerevisiae. Mol Gen Genet. 2000
Jan;262(6):1081-92
Van Hoof C, Janssens V, De Baere I, de Winde JH, Winderickx
J, Dumortier F, Thevelein JM, Merlevede W, Goris J. The
Saccharomyces cerevisiae homologue YPA1 of the
mammalian phosphotyrosyl phosphatase activator of protein
phosphatase 2A controls progression through the G1 phase of
the yeast cell cycle. J Mol Biol. 2000 Sep 8;302(1):103-20
References
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Atlas Genet Cytogenet Oncol Haematol. 2010; 14(1)
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PPP2R4 (protein phosphatase 2A activator, regulatory subunit 4)
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This article should be referenced as such:
Janssens V. PPP2R4 (protein phosphatase 2A activator,
regulatory subunit 4). Atlas Genet Cytogenet Oncol Haematol.
2010; 14(1):48-51.
Magnusdottir A, Stenmark P, Flodin S, Nyman T,
Hammarström M, Ehn M, Bakali H MA, Berglund H, Nordlund
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(1)
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