Targeted suppression of MCT-1 attenuates the malignant phenotype through a translational mechanism

Krystyna Mazan-Mamczarz; Patrick Hagner; Bojie Dai; Sharon Corl; Zhenqui Liu; Ron B. Gartenhaus

doi:10.1016/j.leukres.2008.08.012

Targeted suppression of MCT-1 attenuates the malignant phenotype through a translational mechanism

Krystyna Mazan-Mamczarz, Patrick Hagner, Bojie Dai, Sharon Corl, Zhenqui Liu, Ron B. Gartenhaus

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

The MCT-1 oncogene, highly expressed in a subset of non-Hodgkin's lymphomas interacts with the cap complex through its PUA domain. MCT-1 recruits DENR, a SUI1 motif containing protein that promotes translation initiation of cancer-related mRNAs. We reasoned that a PUA-domain mutant protein would repress MCT-1 function and attenuate the malignant phenotype. Human lymphoma cell lines expressing the PUA-domain mutant protein demonstrated reduced anchorage-independent growth and increased susceptibility to apoptosis. Significantly, we identified an altered translational profile in cells expressing the mutant protein. These data further buttress the role of the MCT-1 in lymphomagenesis and support the development of novel therapeutic strategies targeting MCT-1.

Original language	English (US)
Pages (from-to)	474-482
Number of pages	9
Journal	Leukemia Research
Volume	33
Issue number	3
DOIs	https://doi.org/10.1016/j.leukres.2008.08.012
State	Published - Mar 2009

All Science Journal Classification (ASJC) codes

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.leukres.2008.08.012

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@article{605009435276496d916a959435c95201,

title = "Targeted suppression of MCT-1 attenuates the malignant phenotype through a translational mechanism",

abstract = "The MCT-1 oncogene, highly expressed in a subset of non-Hodgkin's lymphomas interacts with the cap complex through its PUA domain. MCT-1 recruits DENR, a SUI1 motif containing protein that promotes translation initiation of cancer-related mRNAs. We reasoned that a PUA-domain mutant protein would repress MCT-1 function and attenuate the malignant phenotype. Human lymphoma cell lines expressing the PUA-domain mutant protein demonstrated reduced anchorage-independent growth and increased susceptibility to apoptosis. Significantly, we identified an altered translational profile in cells expressing the mutant protein. These data further buttress the role of the MCT-1 in lymphomagenesis and support the development of novel therapeutic strategies targeting MCT-1.",

author = "Krystyna Mazan-Mamczarz and Patrick Hagner and Bojie Dai and Sharon Corl and Zhenqui Liu and Gartenhaus, {Ron B.}",

note = "Funding Information: This work was supported by a Merit Review Award from the Department of Veterans Affairs (R.B.G.). We are grateful to Dr. K.G. Becker and the NIH/NIA Microarray Facility for assistance in the preparation and analysis of the microarray data. K.M.M. and P.H. performed research, analyzed data and wrote the paper. B.D. and S.C. performed research. Z.L. analyzed data. R.B.G. designed research, analyzed data and wrote the paper. ",

year = "2009",

month = mar,

doi = "10.1016/j.leukres.2008.08.012",

language = "English (US)",

volume = "33",

pages = "474--482",

journal = "Leukemia Research",

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T1 - Targeted suppression of MCT-1 attenuates the malignant phenotype through a translational mechanism

AU - Mazan-Mamczarz, Krystyna

AU - Hagner, Patrick

AU - Dai, Bojie

AU - Corl, Sharon

AU - Liu, Zhenqui

AU - Gartenhaus, Ron B.

N1 - Funding Information: This work was supported by a Merit Review Award from the Department of Veterans Affairs (R.B.G.). We are grateful to Dr. K.G. Becker and the NIH/NIA Microarray Facility for assistance in the preparation and analysis of the microarray data. K.M.M. and P.H. performed research, analyzed data and wrote the paper. B.D. and S.C. performed research. Z.L. analyzed data. R.B.G. designed research, analyzed data and wrote the paper.

PY - 2009/3

Y1 - 2009/3

N2 - The MCT-1 oncogene, highly expressed in a subset of non-Hodgkin's lymphomas interacts with the cap complex through its PUA domain. MCT-1 recruits DENR, a SUI1 motif containing protein that promotes translation initiation of cancer-related mRNAs. We reasoned that a PUA-domain mutant protein would repress MCT-1 function and attenuate the malignant phenotype. Human lymphoma cell lines expressing the PUA-domain mutant protein demonstrated reduced anchorage-independent growth and increased susceptibility to apoptosis. Significantly, we identified an altered translational profile in cells expressing the mutant protein. These data further buttress the role of the MCT-1 in lymphomagenesis and support the development of novel therapeutic strategies targeting MCT-1.

AB - The MCT-1 oncogene, highly expressed in a subset of non-Hodgkin's lymphomas interacts with the cap complex through its PUA domain. MCT-1 recruits DENR, a SUI1 motif containing protein that promotes translation initiation of cancer-related mRNAs. We reasoned that a PUA-domain mutant protein would repress MCT-1 function and attenuate the malignant phenotype. Human lymphoma cell lines expressing the PUA-domain mutant protein demonstrated reduced anchorage-independent growth and increased susceptibility to apoptosis. Significantly, we identified an altered translational profile in cells expressing the mutant protein. These data further buttress the role of the MCT-1 in lymphomagenesis and support the development of novel therapeutic strategies targeting MCT-1.

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M3 - Article

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AN - SCOPUS:58549083533

SN - 0145-2126

VL - 33

SP - 474

EP - 482

JO - Leukemia Research

JF - Leukemia Research

IS - 3

ER -

Targeted suppression of MCT-1 attenuates the malignant phenotype through a translational mechanism

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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