Securin is a target of the UV response pathway in mammalian cells.
All eukaryotic cells possess elaborate mechanisms to protect genome integrity and ensure survival after DNA damage, ceasing proliferation and granting time for DNA repair. Securin is an inhibitory protein that is bound to a protease called Separase to inhibit sister chromatid separation until the onset of anaphase. At the metaphase-to-anaphase transition, Securin is degraded by the anaphase-promoting complex or cyclosome, and Separase contributes to the release of cohesins from the chromosome, allowing for the segregation of sister chromatids to opposite spindle poles. Here we provide evidence that human Securin (hSecurin) has a novel role in cell cycle arrest after exposure to UV light or ionizing radiation. In fact, irradiation downregulated the level of hSecurin protein, accelerating its degradation via the proteasome and reducing hSecurin mRNA translation, but the presence of hSecurin is necessary for cell proliferation arrest following UV treatment. Moreover, an alteration of UV-induced hSecurin downregulation could lead directly to the accumulation of DNA damage and the subsequent development of malignant tumors.
Romero
Francisco
F
Departamento de Microbiología, Facultad de Biología, Universidad de Sevilla, 41013 Seville Spain. frport@us.es
Gil-Bernabé
Ana M
AM
Sáez
Carmen
C
Japón
Miguel A
MA
Pintor-Toro
José A
JA
Tortolero
María
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002110:Caffeine / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002460:Cell Line / Q000528:radiation effects; D002469:Cell Separation; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004249:DNA Damage; D010450:Endopeptidases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D064249:Securin; D064247:Separase; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D014965:X-Rays
D018797:Cell Cycle Proteins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D064249:Securin; D015534:Trans-Activators; C578002:pituitary tumor-transforming protein 1, human; D002110:Caffeine; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C577987:ESPL1 protein, human; D064247:Separase; D046988:Proteasome Endopeptidase Complex