LYL1 degradation by the proteasome is directed by a N-terminal PEST rich site in a phosphorylation-independent manner.
BACKGROUND
The Lymphoblastic leukemia 1 (LYL1) gene is a proto-oncogenic transcription factor found upregulated in patients with T-cell acute lymphoblastic leukemia (T-cell ALL). Initially, the upregulation was described to be as a result of a translocation. However, further studies revealed that transcriptional upregulation of LYL1could also occur without translocations. In addition, post-translational mechanisms, such as protein degradation could influence LYL1 expression as well.


RESULTS
In this study, we considered possible post-translational regulation of Lyl1, and investigated fundamental mechanisms governing LYL1 degradation in cell-based culture assays. We identify a PEST sequence motif located in the N-terminus of LYL1, which determines the efficiency of LYL1 degradation by the proteasome. The absence of the PEST degradation site leads to accumulation or upregulation of LYL1. We also show that LYL1 is phosphorylated by MAPK at S36, and determined that proteasomal degradation of LYL1 occurs in a phosphorylation-independent manner.


CONCLUSIONS
Understanding LYL1 degradation is a step forward not only towards deciphering the normal function and regulation of LYL1, but could suggest post-translational mechanisms for upregulation of LYL1 that may contribute to its oncogenic role.
Lukov
Georgi L
GL
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America.
Goodell
Margaret A
MA
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
D051792:Basic Helix-Loop-Helix Proteins; D020929:Mitogen-Activated Protein Kinase Kinases; D009363:Neoplasm Proteins; D046988:Proteasome Endopeptidase Complex; C086541:LYL1 protein, human