Abstract
Approximately half of human tumors bear p53 mutations (Hollestein et al., 1997). The most prevalent type consists of missense mutations that are frequently accompanied by loss of the remaining wild-type p53 (wt-p53) allele (Hainaut et al., 1997; Levine, 1997). The major site of the p53 mutations is the highly conserved DNA binding core domain (Hussain et al., 1998; Prives et al., 1999). Thus, mutant p53 (mt-p53) proteins are unable to specifically bind DNA and to activate specific wt-p53 target genes. Unlike wt-p53, whose half-life is short, mutant p53 proteins are quite stable and abundantly present in cancer cells. One certain outcome of p53 mutations is the loss of wild type activities such as growth arrest, apoptosis, and differentiation (Michalovitz et al., 1990; Yonish-Rouach et al., 1991; Soddu et al., 1996; Almog et al., 1997). However, at variance with other tumor suppressor genes, cells with p53 mutations maintain expression of the fulllength protein. This may suggest that, at least certain mutant forms of p53 can gain additional functions through which actively contribute to cancer progression (Prives et al., 1999; Sigal et al., 2000; Strano et al., 2001; Bullock et al., 2001). Such evidence is provided by several in vitro and in vivo studies (Haley et al., 1990; Dittmer et al., 1993; Gualberto et al., 1998; Frazier et al., 1998; Li et al., 1998; Blandino et al., 1999; Aas et al., 1996; Irwin et al., 2003; Strano et al., 2003).
| Original language | English |
|---|---|
| Title of host publication | 25 Years of p53 Research |
| Publisher | Springer Netherlands |
| Pages | 223-232 |
| Number of pages | 10 |
| ISBN (Print) | 9781402029226, 9781402029202 |
| DOIs | |
| Publication status | Published - 2005 |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
P73, P63 and mutant P53 : Members of protein complexs floating in cancer cells. / Monti, Olimpia; Damalas, Alexander; Strano, Sabrina; Blandino, Giovanni.
25 Years of p53 Research. Springer Netherlands, 2005. p. 223-232.Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - P73, P63 and mutant P53
T2 - Members of protein complexs floating in cancer cells
AU - Monti, Olimpia
AU - Damalas, Alexander
AU - Strano, Sabrina
AU - Blandino, Giovanni
PY - 2005
Y1 - 2005
N2 - Approximately half of human tumors bear p53 mutations (Hollestein et al., 1997). The most prevalent type consists of missense mutations that are frequently accompanied by loss of the remaining wild-type p53 (wt-p53) allele (Hainaut et al., 1997; Levine, 1997). The major site of the p53 mutations is the highly conserved DNA binding core domain (Hussain et al., 1998; Prives et al., 1999). Thus, mutant p53 (mt-p53) proteins are unable to specifically bind DNA and to activate specific wt-p53 target genes. Unlike wt-p53, whose half-life is short, mutant p53 proteins are quite stable and abundantly present in cancer cells. One certain outcome of p53 mutations is the loss of wild type activities such as growth arrest, apoptosis, and differentiation (Michalovitz et al., 1990; Yonish-Rouach et al., 1991; Soddu et al., 1996; Almog et al., 1997). However, at variance with other tumor suppressor genes, cells with p53 mutations maintain expression of the fulllength protein. This may suggest that, at least certain mutant forms of p53 can gain additional functions through which actively contribute to cancer progression (Prives et al., 1999; Sigal et al., 2000; Strano et al., 2001; Bullock et al., 2001). Such evidence is provided by several in vitro and in vivo studies (Haley et al., 1990; Dittmer et al., 1993; Gualberto et al., 1998; Frazier et al., 1998; Li et al., 1998; Blandino et al., 1999; Aas et al., 1996; Irwin et al., 2003; Strano et al., 2003).
AB - Approximately half of human tumors bear p53 mutations (Hollestein et al., 1997). The most prevalent type consists of missense mutations that are frequently accompanied by loss of the remaining wild-type p53 (wt-p53) allele (Hainaut et al., 1997; Levine, 1997). The major site of the p53 mutations is the highly conserved DNA binding core domain (Hussain et al., 1998; Prives et al., 1999). Thus, mutant p53 (mt-p53) proteins are unable to specifically bind DNA and to activate specific wt-p53 target genes. Unlike wt-p53, whose half-life is short, mutant p53 proteins are quite stable and abundantly present in cancer cells. One certain outcome of p53 mutations is the loss of wild type activities such as growth arrest, apoptosis, and differentiation (Michalovitz et al., 1990; Yonish-Rouach et al., 1991; Soddu et al., 1996; Almog et al., 1997). However, at variance with other tumor suppressor genes, cells with p53 mutations maintain expression of the fulllength protein. This may suggest that, at least certain mutant forms of p53 can gain additional functions through which actively contribute to cancer progression (Prives et al., 1999; Sigal et al., 2000; Strano et al., 2001; Bullock et al., 2001). Such evidence is provided by several in vitro and in vivo studies (Haley et al., 1990; Dittmer et al., 1993; Gualberto et al., 1998; Frazier et al., 1998; Li et al., 1998; Blandino et al., 1999; Aas et al., 1996; Irwin et al., 2003; Strano et al., 2003).
UR - http://www.scopus.com/inward/record.url?scp=33646802302&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646802302&partnerID=8YFLogxK
U2 - 10.1007/978-1-4020-2922-6_10
DO - 10.1007/978-1-4020-2922-6_10
M3 - Chapter
AN - SCOPUS:33646802302
SN - 9781402029226
SN - 9781402029202
SP - 223
EP - 232
BT - 25 Years of p53 Research
PB - Springer Netherlands
ER -