Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
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Query: UNIPROT:P05412 (
c-Jun
)
11,453
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In this study, we describe a novel function of the p34(
SEI-1
) protein, which is both an oncogenic protein and a positive regulator of the cell cycle. The p34(
SEI-1
) protein was found to inhibit doxorubicin-induced senescence. We investigated the molecular mechanisms of the inhibitory effect of p34(
SEI-1
) on senescence. First, we found that the activation of protein kinase C-delta (PKC-delta), which is cleaved into a 38 kDa active form from a 78 kDa pro-form, induced after doxorubicin treatment, was inhibited by p34(
SEI-1
). Furthermore, p34(
SEI-1
) induced the ubiquitination of PKC-delta. Yet, there is no interaction between p34(
SEI-1
) and PKC-delta. We also found that the phosphorylation of
c-Jun
-NH(2)-kinase 1 (JNK1) induced after doxorubicin treatment was suppressed by p34(
SEI-1
), but not in JNK2. Consistently, pharmacologic or genetic inactivation of either PKC-delta or JNK1 was found to inhibit doxorubicin-induced senescence. In addition, the genetic inactivation of PKC-delta by PKC-delta small interfering RNA resulted in an inhibition of JNK1 activation, but PKC-delta expression was not inactivated by JNK1 small interfering RNA, implying that the activation of JNK1 could be dependently induced by PKC-delta. Therefore, p34(
SEI-1
) inhibits senescence by inducing PKC-delta ubiquitination and preventing PKC-delta-dependent phosphorylation of JNK1.
...
PMID:p34SEI-1 inhibits doxorubicin-induced senescence through a pathway mediated by protein kinase C-delta and c-Jun-NH2-kinase 1 activation in human breast cancer MCF7 cells. 1990 72
The INK4a-ARF locus plays a central role in the development of pancreatic tumors as evidenced by the fact that up to 98% of pancreatic tumor specimens harbored genetic alterations at the INK4a-ARF locus. Interestingly, in addition to the well-known P16(INK4A) (P16) and P14ARF tumor suppressors, the INK4a-ARF locus in pancreas encodes another protein, P12, whose structure, function, and contributions to pancreatic carcinogenesis remain to be elucidated. In the current study, we demonstrated that over-expression of p12 in human pancreatic cancer cells led to cell arrest at the G1 phase and such cell cycle arrest was related to down-regulation of a number of oncogenes, such as
c-Jun
, Fos, and
SEI1
. Furthermore, unlike P16, P12 did not retain any cyclin-dependent kinase 4 (CDK4)-inhibitory activity. Instead, P12 exhibited a transactivating activity not found in P16. We also examined the genetic status of p12 in a cohort of 40 pancreatic tumor specimens and found that p12 alteration was prevalent in pancreatic tumors with an incidence of 70% (28/40). These results support that P12 is a tumor suppressive protein distinct from P16, and its genetic inactivation is associated with pancreatic carcinogenesis.
...
PMID:Evidence that P12, a specific variant of P16(INK4A), plays a suppressive role in human pancreatic carcinogenesis. 2372 82
