SummaryThe 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 p16 INK4a , p15 INK4b , p18 INK4c , and p19 INK4d , 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.IUBMB Life, 59: 419-426, 2007
Beyond sexual functions, androgens exert their action in skin physiology and pathophysiology. Skin cells are able to synthesize most active androgens from gonadal or adrenal precursors and the enzymes involved in skin steroidogenesis are implicated both in normal or pathological processes. Even when the role of androgens and androgen receptor (AR) in skin pathologies has been studied for decades, their molecular mechanisms in skin disorders remain largely unknown. Here, we analyze recent studies of androgens and AR roles in several skin-related disorders, focusing in the current understanding of their molecular mechanisms in androgenetic alopecia (AGA). We review the molecular pathophysiology of type 2 5α-reductase, AR coactivators, the paracrine factors deregulated in dermal papillae (such as TGF-β, IGF 1, WNTs and DKK-1) and the crosstalk between AR and Wnt signaling in order to shed some light on new promising treatments.
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