Per citar aquest document: http://ddd.uab.cat/record/112619
Expression of arf tumor suppressor in spermatogonia facilitates meiotic progression in male germ cells
Churchman, Michelle L. (Howard Hughes Medical Institute (Memphis, Estats Units d'Amèrica))
Roig Navarro, Ignasi (Universitat Autonoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Jasin, Maria (Memorial Sloan-Kettering Cancer Center (Nova York, Estats Units d'Amèrica))
Keeney, Scott (Howard Hughes Medical Institute (Memphis, Estats Units d'Amèrica))
Sherr, Charles J. (Howard Hughes Medical Institute (Memphis, Estats Units d'Amèrica))

Data: 2011
Resum: The mammalian Cdkn2a (Ink4a-Arf) locus encodes two tumor suppressor proteins (p16Ink4a and p19Arf) that respectively enforce the anti-proliferative functions of the retinoblastoma protein (Rb) and the p53 transcription factor in response to oncogenic stress. Although p19Arf is not normally detected in tissues of young adult mice, a notable exception occurs in the male germ line, where Arf is expressed in spermatogonia, but not in meiotic spermatocytes arising from them. Unlike other contexts in which the induction of Arf potently inhibits cell proliferation, expression of p19Arf in spermatogonia does not interfere with mitotic cell division. Instead, inactivation of Arf triggers germ cell–autonomous, p53-dependent apoptosis of primary spermatocytes in late meiotic prophase, resulting in reduced sperm production. Arf deficiency also causes premature, elevated, and persistent accumulation of the phosphorylated histone variant H2AX, reduces numbers of chromosome-associated complexes of Rad51 and Dmc1 recombinases during meiotic prophase, and yields incompletely synapsed autosomes during pachynema. Inactivation of Ink4a increases the fraction of spermatogonia in S-phase and restores sperm numbers in Ink4a-Arf doubly deficient mice but does not abrogate γ-H2AX accumulation in spermatocytes or p53-dependent apoptosis resulting from Arf inactivation. Thus, as opposed to its canonical role as a tumor suppressor in inducing p53-dependent senescence or apoptosis, Arf expression in spermatogonia instead initiates a salutary feed-forward program that prevents p53-dependent apoptosis, contributing to the survival of meiotic male germ cells.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès.
Document: article ; publishedVersion
Matèria: Cell staining ; Germ cells ; Sperm ; Spermatocytes ; Protein expression ; Spermatogonia
Publicat a: PLoS Genetics, Vol. 7, Issue 7 (July 2011) , p. e1002157, ISSN 1553-7390

DOI: 10.1371/journal.pgen.1002157.


12 p, 6.3 MB

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