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Structure and apoptotic function of p73.

Yoon MK, Ha JH, Lee MS, Chi SW - BMB Rep (2015)

Bottom Line: Like p53, p73 induces apoptosis and cell cycle arrest and transactivates p53-responsive genes, conferring its tumor suppressive activity.In addition, p73 has unique roles in neuronal development and differentiation.In this review, we discuss the p73 structures reported to date, detailed structural comparisons between p73 and p53, and current understanding of the transcription-dependent and -independent mechanisms of p73-induced apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Structural Biology & Nanopore Research Laboratory, Functional Genomics Research Center, KRIBB, Daejeon 305-806, Korea.

ABSTRACT
p73 is a structural and functional homologue of the p53 tumor suppressor protein. Like p53, p73 induces apoptosis and cell cycle arrest and transactivates p53-responsive genes, conferring its tumor suppressive activity. In addition, p73 has unique roles in neuronal development and differentiation. The importance of p73-induced apoptosis lies in its capability to substitute the pro-apoptotic activity of p53 in various human cancer cells in which p53 is mutated or inactive. Despite the great importance of p73-induced apoptosis in cancer therapy, little is known about the molecular basis of p73-induced apoptosis. In this review, we discuss the p73 structures reported to date, detailed structural comparisons between p73 and p53, and current understanding of the transcription-dependent and -independent mechanisms of p73-induced apoptosis.

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Proposed mechanism for transcription-independent p73-induced apoptosis. p73 induces apoptosis by acting directly within the cytoplasm and mitochondria, independent of its transcriptional activity. p73 requires a mediator to trigger apoptosis in some mechanisms but not in others. It is unclear whether Wwox proceeds via the mitochondrial apoptotic pathway (dotted arrow).
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Figure 004: Proposed mechanism for transcription-independent p73-induced apoptosis. p73 induces apoptosis by acting directly within the cytoplasm and mitochondria, independent of its transcriptional activity. p73 requires a mediator to trigger apoptosis in some mechanisms but not in others. It is unclear whether Wwox proceeds via the mitochondrial apoptotic pathway (dotted arrow).

Mentions: Contrary to the observation that p73 is localized and remains within the nucleus during apoptosis (48), accumulating evidence indicate that it is also localized in the cytosol and mitochondria during apoptosis, suggesting direct, exonuclear apoptotic roles of p73, independent of its transcriptional activities. The following sections describe several mediators of transcription-independent apoptosis induced by p73 (Fig. 4).


Structure and apoptotic function of p73.

Yoon MK, Ha JH, Lee MS, Chi SW - BMB Rep (2015)

Proposed mechanism for transcription-independent p73-induced apoptosis. p73 induces apoptosis by acting directly within the cytoplasm and mitochondria, independent of its transcriptional activity. p73 requires a mediator to trigger apoptosis in some mechanisms but not in others. It is unclear whether Wwox proceeds via the mitochondrial apoptotic pathway (dotted arrow).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4352617&req=5

Figure 004: Proposed mechanism for transcription-independent p73-induced apoptosis. p73 induces apoptosis by acting directly within the cytoplasm and mitochondria, independent of its transcriptional activity. p73 requires a mediator to trigger apoptosis in some mechanisms but not in others. It is unclear whether Wwox proceeds via the mitochondrial apoptotic pathway (dotted arrow).
Mentions: Contrary to the observation that p73 is localized and remains within the nucleus during apoptosis (48), accumulating evidence indicate that it is also localized in the cytosol and mitochondria during apoptosis, suggesting direct, exonuclear apoptotic roles of p73, independent of its transcriptional activities. The following sections describe several mediators of transcription-independent apoptosis induced by p73 (Fig. 4).

Bottom Line: Like p53, p73 induces apoptosis and cell cycle arrest and transactivates p53-responsive genes, conferring its tumor suppressive activity.In addition, p73 has unique roles in neuronal development and differentiation.In this review, we discuss the p73 structures reported to date, detailed structural comparisons between p73 and p53, and current understanding of the transcription-dependent and -independent mechanisms of p73-induced apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Structural Biology & Nanopore Research Laboratory, Functional Genomics Research Center, KRIBB, Daejeon 305-806, Korea.

ABSTRACT
p73 is a structural and functional homologue of the p53 tumor suppressor protein. Like p53, p73 induces apoptosis and cell cycle arrest and transactivates p53-responsive genes, conferring its tumor suppressive activity. In addition, p73 has unique roles in neuronal development and differentiation. The importance of p73-induced apoptosis lies in its capability to substitute the pro-apoptotic activity of p53 in various human cancer cells in which p53 is mutated or inactive. Despite the great importance of p73-induced apoptosis in cancer therapy, little is known about the molecular basis of p73-induced apoptosis. In this review, we discuss the p73 structures reported to date, detailed structural comparisons between p73 and p53, and current understanding of the transcription-dependent and -independent mechanisms of p73-induced apoptosis.

Show MeSH
Related in: MedlinePlus