Biomol Ther.  2019 Feb;27(2):231-239. 10.4062/biomolther.2019.021.

Suppressor of Variegation 3–9 Homolog 2, a Novel Binding Protein of Translationally Controlled Tumor Protein, Regulates Cancer Cell Proliferation

• Kim AR
• Sung JY
• Rho SB
• Kim YN
• Yoon K

• KMID: 2442016
• DOI: http://doi.org/10.4062/biomolther.2019.021

Abstract

Suppressor of Variegation 3-9 Homolog 2 (SUV39H2) methylates the lysine 9 residue of histone H3 and induces heterochromatin formation, resulting in transcriptional repression or silencing of target genes. SUV39H1 and SUV39H2 have a role in embryonic development, and SUV39H1 was shown to suppress cell cycle progression associated with Rb. However, the function of human SUV39H2 has not been extensively studied. We observed that forced expression of SUV39H2 decreased cell proliferation by inducing G1 cell cycle arrest. In addition, SUV39H2 was degraded through the ubiquitin-proteasomal pathway. Using yeast two-hybrid screening to address the degradation mechanism and function of SUV39H2, we identified translationally controlled tumor protein (TCTP) as an SUV39H2-interacting molecule. Mapping of the interacting regions indicated that the N-terminal 60 amino acids (aa) of full-length SUV39H2 and the C-terminus of TCTP (120-172 aa) were critical for binding. The interaction of SUV39H2 and TCTP was further confirmed by co-immunoprecipitation and immunofluorescence staining for colocalization. Moreover, depletion of TCTP by RNAi led to up-regulation of SUV39H2 protein, while TCTP overexpression reduced SUV39H2 protein level. The half-life of SUV39H2 protein was significantly extended upon TCTP depletion. These results clearly indicate that TCTP negatively regulates the expression of SUV39H2 post-translationally. Furthermore, SUV39H2 induced apoptotic cell death in TCTP-knockdown cells. Taken together, we identified SUV39H2, as a novel target protein of TCTP and demonstrated that SUV39H2 regulates cell proliferation of lung cancer cells.

Keyword

Histone methyltransferase; SUV39H2; TCTP; Apoptosis; Cell cycle

MeSH Terms

Amino Acids
Apoptosis
Carrier Proteins*
Cell Cycle
Cell Death
Cell Proliferation*
Embryonic Development
Female
Fluorescent Antibody Technique
G1 Phase Cell Cycle Checkpoints
Half-Life
Heterochromatin
Histones
Humans
Immunoprecipitation
Lung Neoplasms
Lysine
Mass Screening
Pregnancy
Repression, Psychology
RNA Interference
Up-Regulation
Yeasts
Amino Acids
Carrier Proteins
Heterochromatin
Histones
Lysine