Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis.
The programmed cell death-10 (PDCD10; also known as cerebral cavernous malformation-3 or CCM3) gene encodes an evolutionarily conserved protein associated with cell apoptosis. Mutations in PDCD10 result in cerebral cavernous malformations, an important cause of cerebral hemorrhage. PDCD10 is associated with serine/threonine kinases and phosphatases and modulates the extracellular signal-regulated kinase pathway suggesting a role in the regulation of cellular growth. Here we provide evidence of a constitutive expression of PDCD10 in malignant T cells and cell lines from peripheral blood of cutaneous T-cell lymphoma (Sezary syndrome) patients. PDCD10 is associated with protein phosphatase-2A, a regulator of mitogenesis and apoptosis in malignant T cells. Inhibition of oncogenic signal pathways [Jak3, Notch1, and nuclear factor-κB (NF-κB)] partly inhibits the constitutive PDCD10 expression, whereas an activator of Jak3 and NF-κB, interleukin-2 (IL-2), enhances PDCD10 expression. Functional data show that PDCD10 depletion by small interfering RNA induces apoptosis and decreases proliferation of the sensitive cells. To our knowledge, these data provide the first functional link between PDCD10 and cancer.
Lauenborg
Britt
B
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Kopp
Katharina
K
Krejsgaard
Thorbjørn
T
Eriksen
Karsten W
KW
Geisler
Carsten
C
Dabelsteen
Sally
S
Gniadecki
Robert
R
Zhang
Qian
Q
Wasik
Mariusz A
MA
Woetmann
Anders
A
Odum
Niels
N
D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D054648:Protein Phosphatase 2 / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012751:Sezary Syndrome / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology*; D012878:Skin Neoplasms / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D012313:RNA; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2