PMID- 9529248
OWN - NLM
STAT- MEDLINE
DCOM- 19980413
LR  - 20190705
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 92
IP  - 6
DP  - 1998 Mar 20
TI  - The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and 
      neutralizes MDM2's inhibition of p53.
PG  - 713-23
AB  - The INK4a gene encodes two distinct growth inhibitors--the cyclin-dependent 
      kinase inhibitor p16Ink4a, which is a component of the Rb pathway, and the tumor 
      suppressor p19Arf, which has been functionally linked to p53. Here we show that 
      p19Arf potently suppresses oncogenic transformation in primary cells and that 
      this function is abrogated when p53 is neutralized by viral oncoproteins and 
      dominant-negative mutants but not by the p53 antagonist MDM2. This finding, 
      coupled with the observations that p19Arf and MDM2 physically interact and that 
      p19Rrf blocks MDM2-induced p53 degradation and transactivational silencing, 
      suggests that p19Arf functions mechanistically to prevent MDM2's neutralization 
      of p53. Together, our findings ascribe INK4a's potent tumor suppressor activity 
      to the cooperative actions of its two protein products and their relation to the 
      two central growth control pathways, Rb and p53.
FAU - Pomerantz, J
AU  - Pomerantz J
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, New York 10461, USA.
FAU - Schreiber-Agus, N
AU  - Schreiber-Agus N
FAU - Liegeois, N J
AU  - Liegeois NJ
FAU - Silverman, A
AU  - Silverman A
FAU - Alland, L
AU  - Alland L
FAU - Chin, L
AU  - Chin L
FAU - Potes, J
AU  - Potes J
FAU - Chen, K
AU  - Chen K
FAU - Orlow, I
AU  - Orlow I
FAU - Lee, H W
AU  - Lee HW
FAU - Cordon-Cardo, C
AU  - Cordon-Cardo C
FAU - DePinho, R A
AU  - DePinho RA
LA  - eng
GR  - CA47179/CA/NCI NIH HHS/United States
GR  - CA47538/CA/NCI NIH HHS/United States
GR  - CADK97650/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Deoxyuracil Nucleotides)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Suppressor Protein p14ARF)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 6SO6U10H04 (Biotin)
RN  - EC 2.3.2.27 (Mdm2 protein, mouse)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Biotin
MH  - Cell Line/chemistry/cytology/physiology
MH  - DNA Fragmentation
MH  - Deoxyuracil Nucleotides
MH  - Genes, p16/*physiology
MH  - Lens, Crystalline/cytology
MH  - Mice
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - *Nuclear Proteins
MH  - Osteoblasts/chemistry/cytology/physiology
MH  - Proteins/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-mdm2
MH  - Retinoblastoma Protein/metabolism
MH  - Staining and Labeling
MH  - Transformation, Genetic
MH  - Tumor Suppressor Protein p14ARF
MH  - Tumor Suppressor Protein p53/*metabolism
EDAT- 1998/04/07 00:00
MHDA- 1998/04/07 00:01
CRDT- 1998/04/07 00:00
PHST- 1998/04/07 00:00 [pubmed]
PHST- 1998/04/07 00:01 [medline]
PHST- 1998/04/07 00:00 [entrez]
AID - S0092-8674(00)81400-2 [pii]
AID - 10.1016/s0092-8674(00)81400-2 [doi]
PST - ppublish
SO  - Cell. 1998 Mar 20;92(6):713-23. doi: 10.1016/s0092-8674(00)81400-2.