Functions, divergence and clinical value of TAp73 isoforms in cancer

Logotheti S., Pavlopoulou A., Galtsidis S., Vojtesek B., Zoumpourlis V.

CANCER AND METASTASIS REVIEWS, cilt.32, sa.3-4, ss.511-534, 2013 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 32 Sayı: 3-4
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1007/s10555-013-9424-x
  • Dergi Adı: CANCER AND METASTASIS REVIEWS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.511-534
  • Anahtar Kelimeler: TAp73 isoforms, C terminus, Cancer, DNA damage, Apoptosis, Cell cycle arrest, P73 SPLICING VARIANTS, KINASE C-ABL, DNA-DAMAGE, TRANSCRIPTIONAL ACTIVITY, PHYSICAL INTERACTION, P53 FAMILY, APOPTOTIC RESPONSE, DOWN-REGULATION, CELL-CYCLE, DIFFERENTIAL EXPRESSION
  • Dokuz Eylül Üniversitesi Adresli: Hayır

Özet

The p73 gene encodes the tumour suppressive full-length TAp73 and N-terminal-truncated DNp73 isoforms that act as dominant negative inhibitors of TAp73. The overall effect of p73 in oncogenesis is thought to depend on the TAp73 to DNp73 isoforms' ratio. TAp73 isoforms include a number of C-terminal variants as a result of alternative splicing in 3'-end. TAp73 isoforms protect cells from oncogenic alterations in a multifaceted way since they are implicated in the suppression of all demonstrated hallmarks and enabling characteristics of cancer. Their best established role is in apoptosis, a process which seems to be differently affected by each TAp73 C-terminal variant. Based on previous findings and our thorough bioinformatics analysis, we highlight that TAp73 variants are functionally non-equivalent, since they present major differences in their transactivation efficiencies, protein interactions, response to DNA damage and apoptotic effects that are attributable to the primary structure of their C terminus. In this review, we summarise these differences and we unveil the link between crucial C-terminal motifs/residues and the oncosuppressive potential of TAp73 isoforms, emphasising on the importance of considering C terminus during the development of p73-based anticancer biologics.