title: DNA damage induced activation of Cygb stabilizes p53 and mediates G1 arrest.
abstract: Cytoglobin (Cygb) is an emerging tumor suppressor gene silenced by promoter hypermethylation in many human tumors. So far, the precise molecular mechanism underlying its tumor suppressive function remains poorly understood. Here, we identified Cygb as a genotoxic stress-responsive hemoprotein upregulated upon sensing cellular DNA damage. Our studies demonstrated that Cygb physically associates with and stabilizes p53, a key cellular DNA damage signaling factor. We provide evidence that Cygb extends the half-life of p53 by blocking its ubiquitination and subsequent degradation. We show that, upon DNA damage, cells overexpressing Cygb displayed proliferation defect by rapid accumulation of p53 and its target gene p21, while Cygb knockdown cells failed to efficiently arrest in G1 phase in response to DNA insult. These results suggest a possible involvement of Cygb in mediating cellular response to DNA damage and thereby contributing in the maintenance of genomic integrity. Our study thus presents a novel insight into the mechanistic role of Cygb in tumor suppression.
authors.affiliation: Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, Dhaula Kuan, New Delhi 110021, India.
authors.forename: Rince
authors.initials: R
authors.lastname: John
authors.affiliation: Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, Dhaula Kuan, New Delhi 110021, India.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Chand
authors.affiliation: Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, Dhaula Kuan, New Delhi 110021, India.
authors.forename: Sankalpa
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, Dhaula Kuan, New Delhi 110021, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Jaiswal
authors.affiliation: Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, Dhaula Kuan, New Delhi 110021, India. Electronic address: alonag22@gmail.com.
authors.forename: Alo
authors.initials: A
authors.lastname: Nag
mesh_terms: D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D000078842:Cytoglobin; D004249:DNA Damage / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005914:Globins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells / Q000187:drug effects; D006801:Humans; D055550:Protein Stability; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C493956:CDKN1A protein, human; C000627265:CYGB protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D000078842:Cytoglobin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D004317:Doxorubicin; D005914:Globins
keywords: Cell cycle arrest; Cygb; DNA damage; Tumor suppressor; p53