Download Gene Section PDCD4 (programmed cell death 4) Atlas of Genetics and Cytogenetics

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Gene Section
Mini Review
PDCD4 (programmed cell death 4)
Nancy H Colburn
Laboratory of Cancer Prevention, National Cancer Institute, Bldg. 576, Rm. 101, Frederick, MD 217021201, USA
Published in Atlas Database: August 2007
Online updated version: http://AtlasGeneticsOncology.org/Genes/PDCD4ID41675ch10q24.html
DOI: 10.4267/2042/38497
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 2008 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
that programs PDCD4
proteasome degradation.
for
ubiquitylation
and
Hugo: PDCD4
Other names: TIS; H731; DUG; MA3
Location: 10q24
Localisation
DNA/RNA
Function
Description
PDCD4 inhibits translation initiation mRNAspecifically by interacting with translation initiation
factor eIF4A and competing with eIF4Gc for binding to
eIF4A. As a consequence of inhibiting translation
initiation, inhibits AP-1 dependent transcription via
targeting Jun kinase signaling. Found to be a tumor
suppressor in PDCD4 transgenic and deficient mice.
Nuclear and cytoplasmic. Inhibits translation in
cytoplasm.
Single gene of 11 exons spanning 21 kbp.
Transcription
2.4 Kb mRNA; PDCD4 mRNA levels modulated by
apoptosis inducers, retinoids, and other extracellular
signals.
Homology
Pseudogene
Conserved MA3 domain also found in translation
initiation factor eIF4G, a scaffold protein; death
associated protein DAP5; and NOM 1, a nucleolar
protein.
None.
Protein
Mutations
Note: No evidence for mutational inactivation in
cancer.
Description
Implicated in
469 amino acids; 52 kDa predicted; found to be 50-64
kDa in mouse and human tissues and cell lines;
contains two highly conserved helical MA3 domains
each about 130 amino acids long; contains two
Akt/S6K phosphorylation sites, one N-terminal and one
C-terminal; contains two nuclear export signals.
Human tumors
Disease
PDCD4 expression attenuated with progression in
human tumors of the lung, colon, prostate and breast;
diagnostic and prognostic for colon cancer staging with
decreased expression in adenomas and a further
decrease in stage 1 adenocarcinomas. Transgenic
PDCD4 expression attenuates skin tumorigenesis and
tumor progression in transgenic mice; PDCD4
deficiency increases tumor multiplicity and tumor
incidence.
Expression
PDCD4 expressed in all tissues tested. Shows inverse
expression with proliferation marker PCNA, higher
expression in differentiated areas. Protein expression is
regulated by PI3K/Akt/S6K and MEK/ERK signaling
Atlas Genet Cytogenet Oncol Haematol. 2008;12(2)
125
PDCD4 (programmed cell death 4)
Colburn NH
Palamarchuk A, Efanov A, Maximov V, Aqeilan RI, Croce CM,
Pekarsky Y. Akt phosphorylates and regulates Pdcd4 tumor
suppressor protein. Cancer Res 2005;65(24):11282-11286.
References
Azzoni L, Zatsepina O, Abebe B, Bennett IM, Kanakaraj P,
Perussia B. Differential transcriptional regulation of CD161 and
a novel gene, 197/15a, by IL-2, IL-15, and IL-12 in NK and T
cells. J Immunol 1998;161(7):3493-3500.
Dorrello NV, Peschiaroli A, Guardavaccaro D, Colburn NH,
Sherman NE, Pagano M. S6K1- and betaTRCP-mediated
degradation of PDCD4 promotes protein translation and cell
growth. Science 2006;314(5798):467-471.
Cmarik JL, Min H, Hegamyer G, Zhan S, Kulesz-Martin M,
Yoshinaga H, Matsuhashi S, Colburn NH. Differentially
expressed protein Pdcd4 inhibits tumor promoter-induced
neoplastic transformation. Proc Natl Acad Sci USA
1999;96(24):14037-14042.
Hilliard A, Hilliard B, Zheng SJ, Sun H, Miwa T, Song W, Göke
R, Chen YH. Translational regulation of autoimmune
inflammation and lymphoma genesis by programmed cell
death 4. J Immunol 2006;177(11):8095-8102.
Schlichter U, Burk O, Worpenberg S, Klempnauer KH. The
chicken Pdcd4 gene is regulated by v-Myb. Oncogene
2001;20(2):231-239.
Jin H, Kim TH, Hwang SK, Chang SH, Kim HW, Anderson HK,
Lee HW, Lee KH, Colburn NH, Yang HS, Cho MH, Cho CS.
Aerosol
delivery
of
urocanic
acid-modified
chitosan/programmed cell death 4 complex regulated
apoptosis, cell cycle, and angiogenesis in lungs of K-ras null
mice. Mol Cancer Ther 2006;5(4):1041-1049.
Yang HS, Jansen AP, Nair R, Shibahara K, Verma AK, Cmarik
JL, Colburn NH. A novel transformation suppressor, Pdcd4,
inhibits AP-1 transactivation but not NF-kappaB or ODC
transactivation. Oncogene 2001;20(6):669-676.
Sonenberg N, Pause A. Signal transduction. Protein synthesis
and oncogenesis meet again. Science 2006;314(5798):428429.
Zhang Z, DuBois RN. Detection of differentially expressed
genes in human colon carcinoma cells treated with a selective
COX-2 inhibitor. Oncogene 2001;20(33):4450-4456.
Yang HS, Matthews CP, Clair T, Wang Q, Baker AR, Li CC,
Tan TH, Colburn NH. Tumorigenesis suppressor Pdcd4 downregulates mitogen-activated protein kinase kinase kinase
kinase 1 expression to suppress colon carcinoma cell invasion.
Mol Cell Biol 2006;26(4):1297-1306.
Appl H, Klempnauer KH. Targeted disruption of c-myb in the
chicken pre B-cell line DT40. Oncogene 2002;21(19):30763081.
Böhm M, Sawicka K, Siebrasse JP, Brehmer-Fastnacht A,
Peters R, Klempnauer KH. The transformation suppressor
protein Pdcd4 shuttles between nucleus and cytoplasm and
binds RNA. Oncogene 2003;22(31):4905-4910.
Zhang H, Ozaki I, Mizuta T, Hamajima H, Yasutake T, Eguchi
Y, Ideguchi H, Yamamoto K, Matsuhashi S. Involvement of
programmed cell death 4 in transforming growth factor-beta1induced apoptosis in human hepatocellular carcinoma.
Oncogene 2006;25(45):6101-6112.
Chen Y, Knösel T, Kristiansen G, Pietas A, Garber ME,
Matsuhashi S, Ozaki I, Petersen I. Loss of PDCD4 expression
in human lung cancer correlates with tumour progression and
prognosis. J Pathol 2003;200(5):640-646.
LaRonde-LeBlanc N, Santhanam AN, Baker AR, Wlodawer A,
Colburn NH. Structural basis for inhibition of translation by the
tumor suppressor Pdcd4. Mol Cell Biol 2007;27(1):147-156.
Yang HS, Jansen AP, Komar AA, Zheng X, Merrick WC,
Costes S, Lockett SJ, Sonenberg N, Colburn NH. The
transformation suppressor Pdcd4 is a novel eukaryotic
translation initiation factor 4A binding protein that inhibits
translation. Mol Cell Biol 2003;23(1):26-37.
Leupold JH, Yang HS, Colburn NH, Asangani I, Post S,
Allgayer
H.
Tumor
suppressor
Pdcd4
inhibits
invasion/intravasation and regulates urokinase receptor (uPAR) gene expression via Sp-transcription factors. Oncogene
2007;26(31):4550-4562.
Yang HS, Knies JL, Stark C, Colburn NH. Pdcd4 suppresses
tumor phenotype in JB6 cells by inhibiting AP-1 transactivation.
Oncogene 2003;22(24):3712-3720.
Ozpolat B, Akar U, Steiner M, Zorrilla-Calancha I, TiradoGomez M, Colburn N, Danilenko M, Kornblau S, Berestein GL.
Programmed cell death-4 tumor suppressor protein contributes
to retinoic acid-induced terminal granulocytic differentiation of
human myeloid leukemia cells. Mol Cancer Res 2007;5(1):95108.
Young MR, Yang HS, Colburn NH. Promising molecular
targets for cancer prevention: AP-1, NF-kappa B and Pdcd4.
Trends Mol Med 2003;9(1):36-41. (Review).
Waters LC, Veverka V, Böhm M, Schmedt T, Choong PT,
Muskett FW, Klempnauer KH, Carr MD. Structure of the Cterminal MA-3 domain of the tumour suppressor protein Pdcd4
and characterization of its interaction with eIF4A. Oncogene
2007;26(34):4941-4950.
Jansen AP, Camalier CE, Stark C, Colburn NH.
Characterization of programmed cell death 4 in multiple human
cancers reveals a novel enhancer of drug sensitivity. Mol
Cancer Ther 2004;3(2):103-110.
Yang HS, Cho MH, Zakowicz H, Hegamyer G, Sonenberg N,
Colburn NH. A novel function of the MA-3 domains in
transformation and translation suppressor Pdcd4 is essential
for its binding to eukaryotic translation initiation factor 4A. Mol
Cell Biol 2004;24(9):3894-3906.
This article should be referenced as such:
Colburn NH. PDCD4 (programmed cell death 4). Atlas Genet
Cytogenet Oncol Haematol. 2008;12(2):125-126.
Jansen AP, Camalier CE, Colburn NH. Epidermal expression
of the translation inhibitor programmed cell death 4 suppresses
tumorigenesis. Cancer Res 2005;65(14):6034-6041.
Atlas Genet Cytogenet Oncol Haematol. 2008;12(2)
126