INVESTIGADORES
OGARA Maria Florencia
artículos
Título:
INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions?
Autor/es:
CÁNEPA, E.T.; SCASSA, M. E.; CERUTI, J. M.; MARAZITA M.C.; CARCAGNO A.L.; SIRKIN P.F.; OGARA M.F.
Revista:
IUBMB LIFE
Editorial:
Taylor and Francis Inc.
Referencias:
Lugar: Philadelphia; Año: 2007 vol. 59 p. 419 - 426
ISSN:
1521-6543
Resumen:
The cyclin D-Cdk4-6/INK4/Rb/E2F pathway plays a key role
in controlling cell growth by integrating multiple mitogenic and
antimitogenic stimuli. The members of INK4 family, comprising
p16INK4a, p15INK4b, p18INK4c, and p19INK4d, block the progression
of the cell cycle by binding to either Cdk4 or Cdk6 and inhibiting
the action of cyclin D. These INK4 proteins share a similar
structure dominated by several ankyrin repeats. Although they
appear to be structurally redundant and equally potent as
inhibitors, the INK4 family members are differentially expressed
during mouse development. The striking diversity in the pattern of
expression of INK4 genes suggested that this family of cell cycle
inhibitors might have cell lineage-specific or tissue-specific
functions. The INK4 proteins are commonly lost or inactivated
by mutations in diverse types of cancer, and they represent
established or candidate tumor suppressors. Apart from their
capacity to arrest cells in the G1-phase of the cell cycle they have
been shown to participate in an increasing number of cellular
processes. Given their emerging roles in fundamental physiological
as well as pathological processes, it is interesting to explore
the diverse roles for the individual INK4 family members in
different functions other than cell cycle regulation. Extensive
studies, over the past few years, uncover the involvement of INK4
proteins in senescence, apoptosis, DNA repair, and multistep
oncogenesis. We will focus the discussion here on these
unexpected issues.