p21 can be a barrier to ferroptosis independent of p53
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作者:
Venkatesh, Divya
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Columbia Univ, Dept Biol Sci, New York, NY 10027 USAColumbia Univ, Dept Biol Sci, New York, NY 10027 USA
Venkatesh, Divya
[1
]
Stockwell, Brent R.
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Columbia Univ, Dept Biol Sci, New York, NY 10027 USA
Columbia Univ, Dept Chem, New York, NY 10027 USAColumbia Univ, Dept Biol Sci, New York, NY 10027 USA
Stockwell, Brent R.
[1
,2
]
Prives, Carol
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Columbia Univ, Dept Biol Sci, New York, NY 10027 USAColumbia Univ, Dept Biol Sci, New York, NY 10027 USA
Prives, Carol
[1
]
机构:
[1] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA
[2] Columbia Univ, Dept Chem, New York, NY 10027 USA
Traditionally, the p21 protein has been viewed as limiting cancer progression and promoting aging. In contrast, there are reports that p21 can enhance cancer survival and limit tissue damage, depending on the tissue of origin and type of stressor involved. Here, we provide evidence to support these latter two roles of p21 by exploring its ability to regulate ferroptosis. Ferroptosis is a form of cell death that is associated with certain degenerative diseases, some of which are aging-related. Our results reveal a correlation between p21 protein levels in cell lines that are resistant to ferroptosis (p21 high) versus cell lines that are sensitive and easily undergo ferroptosis (p21 low). We also show that p21 levels themselves are differentially regulated in response to ferroptosis in a p53-independent manner. Further, experimentally altering the abundance of p21 protein inverts the ferroptosis-sensitivity of both resistant and sensitive human cancer cell lines. Our data also indicate that the interaction of p21 with CDKs is crucial for its ability to restrict the progression of ferroptosis. While this study was performed in cancer cell lines, our results support the potential of p21 to aid in maintenance of healthy tissues by blocking the damage incurred due to ferroptosis.
机构:
Comenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, SlovakiaComenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, Slovakia
Sivonova, Monika Kmetova
Vilckova, Marta
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Comenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, SlovakiaComenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, Slovakia
Vilckova, Marta
Kliment, Jan
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Comenius Univ, Jessenius Fac Med, Dept Urol, Martin 03601, Slovakia
UHM, Martin 03601, SlovakiaComenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, Slovakia
Kliment, Jan
Mahmood, Silvia
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Comenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, SlovakiaComenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, Slovakia
Mahmood, Silvia
Jurecekova, Jana
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Comenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, SlovakiaComenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, Slovakia
Jurecekova, Jana
Dusenkova, Svetlana
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Comenius Univ, Jessenius Fac Med, Dept Urol, Martin 03601, Slovakia
UHM, Martin 03601, SlovakiaComenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, Slovakia
Dusenkova, Svetlana
Waczulikova, Iveta
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Comenius Univ, Fac Math Phys & Informat, Div Biomed Phys, Dept Nucl Phys & Biophys, Bratislava 84248, SlovakiaComenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, Slovakia
Waczulikova, Iveta
Slezak, Peter
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Comenius Univ, Fac Med, Inst Simulat & Virtual Med Educ, Bratislava 81372, SlovakiaComenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, Slovakia
Slezak, Peter
Dobrota, Dusan
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Comenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, SlovakiaComenius Univ, Jessenius Fac Med, Dept Med Biochem, Mala Hora 4, Martin 03601, Slovakia