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Expression of a p16 INK4a ‐specific ribozyme downmodulates p16 INK4a abundance and accelerates cell proliferation
Author(s) -
Nylandsted Jesper,
Rohde Mikkel,
Bartek Jiri,
Strauss Michael
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01089-8
Subject(s) - ribozyme , hammerhead ribozyme , biology , cell cycle , cell growth , microbiology and biotechnology , senescence , rna , cell , gene , genetics
The p16 INK4a tumor suppressor negatively regulates progression through the G1 phase of the mammalian cell cycle. To mimic the downmodulation of p16 INK4a commonly seen in cancer, we designed and characterized a hammerhead ribozyme against exon E1α of the murine p16 INK4a transcript. Stable expression of the ribozyme in murine erythroleukemia (MEL) cells reduced the endogenous p16 INK4a protein by more than 70% and significantly accelerated cell cycle progression. The specificity and efficiency of our new ribozyme suggest its possible application in elucidating the role of p16 INK4a in fundamental biological processes including homeostatic tissue renewal, protection against oncogenic transformation, and cellular senescence.