PMID- 10445844
OWN - NLM
STAT- MEDLINE
DCOM- 19990907
LR  - 20081121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 26
DP  - 1999 Jul 1
TI  - Tissue-specific alternative splicing in the human INK4a/ARF cell cycle regulatory
      locus.
PG  - 3810-20
AB  - The INK4a/ARF locus on human chromosome 9p resides at the nexus of two critical
      cell cycle regulatory pathways, the p53 pathway and the retinoblastoma (pRb) gene
      pathway. Through the use of shared coding regions and alternative reading frames 
      two distinct proteins are produced: INK4a is a cyclin-dependent kinase inhibitor 
      whereas ARF binds the MDM2 proto-oncogene and stabilizes p53. We have examined
      the expression patterns of the INK4a/ARF locus at the RNA level in normal human
      and murine tissues to determine if these genes are coordinately regulated. We
      found that both INK4a and ARF were expressed in most tissues at low levels
      detectable only by RT-PCR. The pancreas was an exception in that it expressed no 
      detectable ARF mRNA but expressed high levels of INK4a mRNA. Furthermore, human
      pancreas expressed an additional previously unrecognized splice variant of INK4a,
      termed p12, through the use of an alternative splice donor site within intron 1. 
      The p12 transcript produced a 12 kD protein composed of INK4a exon 1alpha and a
      novel intron-derived C-terminus. This novel protein did not interact with cdk4
      but was capable of suppressing growth in a pRb-independent manner. The
      implications of the capacity of the INK4a/ARF locus to encode a third transcript,
      and for pancreatic cancer, in which the INK4a/ARF locus is nearly always altered,
      are considered.
FAU - Robertson, K D
AU  - Robertson KD
AD  - USC/Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
FAU - Jones, P A
AU  - Jones PA
LA  - eng
GR  - R35 CA 49758-09/CA/NCI NIH HHS/United States
GR  - T32 CA 09320-15/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA, Complementary)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Cycle/*genetics
MH  - Cell Cycle Proteins/chemistry/genetics/immunology
MH  - Cell Line
MH  - Chromosomes, Human, Pair 9/*genetics
MH  - Cloning, Molecular
MH  - DNA, Complementary/genetics
MH  - Female
MH  - Gene Expression Regulation
MH  - Genes, Retinoblastoma
MH  - *Genes, p16
MH  - Genes, p53
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Organ Specificity
MH  - Pancreas/metabolism
MH  - Pancreatic Neoplasms/genetics/metabolism
MH  - Promoter Regions, Genetic
MH  - *RNA Splicing
MH  - RNA, Messenger/*metabolism
MH  - Reading Frames/*genetics
MH  - Recombinant Fusion Proteins/metabolism
MH  - *Regulatory Sequences, Nucleic Acid
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Alignment
MH  - Sequence Deletion
MH  - Sequence Homology, Nucleic Acid
MH  - Tumor Cells, Cultured
MH  - Uterine Cervical Neoplasms/pathology
EDAT- 1999/08/13 00:00
MHDA- 1999/08/13 00:01
CRDT- 1999/08/13 00:00
PHST- 1999/08/13 00:00 [pubmed]
PHST- 1999/08/13 00:01 [medline]
PHST- 1999/08/13 00:00 [entrez]
AID - 10.1038/sj.onc.1202737 [doi]
PST - ppublish
SO  - Oncogene. 1999 Jul 1;18(26):3810-20. doi: 10.1038/sj.onc.1202737.