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Assessment of SAMD9L protein function in cell cycle progression

Wang, Surui (2019) MOBN03 20182
Degree Projects in Molecular Biology
Popular Abstract
Functional assessment of SAMD9/SAMD9L proteins in cell cycle progression

Myelodysplastic syndromes (MDS) are one of the most neoplasms resulting in defective generation of blood cells. Chromosomal abnormalities are common in MDS, with deletions of chromosome 5 being the most common aberration adult patients while deletions of chromosome 7 are most common in childhood MDS. MDS with loss of chromosome 7 has a poor clinical prognosis, with frequent progression to acute leukemia. SAMD9 and SAMD9L are two evolutionary conserved, very similar genes located on human chromosome 7. The proteins encoded by these two genes are classified as tumor suppressors, since they can block cell proliferation. Mutations in SAMD9 and SAMD9L are associated... (More)
Functional assessment of SAMD9/SAMD9L proteins in cell cycle progression

Myelodysplastic syndromes (MDS) are one of the most neoplasms resulting in defective generation of blood cells. Chromosomal abnormalities are common in MDS, with deletions of chromosome 5 being the most common aberration adult patients while deletions of chromosome 7 are most common in childhood MDS. MDS with loss of chromosome 7 has a poor clinical prognosis, with frequent progression to acute leukemia. SAMD9 and SAMD9L are two evolutionary conserved, very similar genes located on human chromosome 7. The proteins encoded by these two genes are classified as tumor suppressors, since they can block cell proliferation. Mutations in SAMD9 and SAMD9L are associated with inherited forms of MDS with deletions of chromosome 7.

In this project, we aim to find out the mechanism behind the growth inhibitory effect of SAMD9 and SAMD9L proteins through functional assays performed in the test tube. Different SAMD9L variants proteins, some associated with genetic disease, were expressed in different cell lines. Regulation of cell cycle an overall protein synthesis was quantified using different cellular approaches.

Forced expression of wild type SAMD9L were found to exhibit a moderate inhibition on DNA as well as protein synthesis, while disease-associated mutants completely blocked cell proliferation. A core part of the protein mediating anti-proliferative activity was identified. We also deduced that the anti-proliferative activity was independent of a common pathway for restricting cell cycle entry, but rather relied on effective inhibition of protein synthesis.

Our results provide new molecular insights to how SAMD9 and SAMD9L act to restrict cell proliferation. These insights partly explain how these proteins may act in controlling virus infections. They could also help us understand the pathogenesis of monosomy 7 towards MDS and provide possible therapies.


Master’s Degree Project in Molecular Biology 60 credits 2019
Department of Biology, Lund University

Advisor: Yenan Bryceson
Advisors Unit/Department: Center for Hematology and Regenerative Medicine, Karolinska Institutet. (Less)
Please use this url to cite or link to this publication:
author
Wang, Surui
supervisor
organization
course
MOBN03 20182
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8985705
date added to LUP
2019-06-19 08:48:45
date last changed
2019-06-19 08:48:45
@misc{8985705,
  author       = {{Wang, Surui}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Assessment of SAMD9L protein function in cell cycle progression}},
  year         = {{2019}},
}