Tankyrase 1 regulates centrosome function by controlling CPAP stability.

CPAP--a gene mutated in primary microcephaly--is required for procentriole formation. Here we show that CPAP degradation and function is controlled by the poly(ADP-ribose) polymerase tankyrase 1. CPAP is PARsylated by tankyrase 1 in vitro and in vivo.

GDP-mannose-4,6-dehydratase is a cytosolic partner of tankyrase 1 that inhibits its poly(ADP-ribose) polymerase activity.

Tankyrase 1 is a poly(ADP-ribose) polymerase (PARP) that participates in a broad range of cellular activities due to interaction with multiple binding partners. Tankyrase 1 recognizes a linear six-amino-acid degenerate motif and, hence, has hundreds of potential target proteins. Binding of partner proteins to tankyrase 1 usually results in their poly(ADP-ribosyl)ation (PARsylation) and can lead to ubiquitylation and proteasomal degradation.

Immunodetection of human telomerase reverse-transcriptase (hTERT) re-appraised: nucleolin and telomerase cross paths.

The involvement of telomerase in cellular immortalization and senescence has often been assessed by means of telomerase expression at the RNA level and quantification of telomerase activity by the telomeric repeat amplification protocol assay. However, these methods either neglected the existence of various telomerase splice variants, or ignored the nonconventional functions of telomerase independent of its ability to elongate and maintain telomere length. Immunodetection of telomerase is now being recognized as a necessary approach to precisely elucidate its roles in oncogenesis and senescence.

[Cell death signalling: recent advances and therapeutic application].

Apoptosis is presently one of the most obvious targets for cancer treatment as its frequent inactivation in tumors contributes to carcinogenesis as well as resistance to chemotherapy. As knowledge of the apoptotic pathways and their regulation increases, it becomes obvious that this regulation is more complex than previously expected. Furthermore, there is growing evidence that alternative signalling pathways for cell death have to be considered.

Death receptor signaling regulatory function for telomerase: hTERT abolishes TRAIL-induced apoptosis, independently of telomere maintenance.

Human telomerase has been implicated in cell immortalization and cancer. Recent works suggest that telomerase confers additional function required for tumorigenesis that does not depend on its ability to maintain telomeres. This new action may influence tumor therapy outcomes by yet unraveled mechanisms.

Retinoic acid receptor alpha and retinoid-X receptor-specific agonists synergistically target telomerase expression and induce tumor cell death.

Retinoids modulate growth and differentiation of cancer cells through activation of gene transcription via the nuclear retinoic-acid receptors (RAR) and retinoid-X receptors (RXR). Their use in differentiation therapy of acute promyelocytic leukemia (APL) represents a model concept for reprogramming cancer cells. However, they also regulate antiproliferative genes whose functions do not mechanistically concur to this program.

Apoptosome-independent pathway for apoptosis. Biochemical analysis of APAF-1 defects and biological outcomes.

Induction and execution of apoptosis programs are generally believed to be mediated through a hierarchy of caspase activation. By using two cellular variants obtained from the L1210 cell line (L1210/S and L1210/0), we have shown previously that staurosporine induces apoptotic cell death through both caspase-dependent and caspase-independent pathways. Both pathways normally coexisted in L1210/S cells, whereas L1210/0 cells lacked the ability to activate caspases despite the confirmed presence of both procaspase-3 and -9.