scholarly journals Over-Expression of p45SKP2 in Kaposi’s Sarcoma Correlates with Higher Tumor Stage and Extracutaneous Involvement but Is Not Directly Related to p27KIP1 Down-Regulation

2002 ◽  
Vol 15 (11) ◽  
pp. 1227-1235 ◽  
Author(s):  
R. M. Penin ◽  
M. T. Fernandez-Figueras ◽  
L. Puig ◽  
J. Rex ◽  
C. Ferrandiz ◽  
...  
2007 ◽  
Vol 81 (12) ◽  
pp. 6573-6583 ◽  
Author(s):  
Robert E. Means ◽  
Sabine M. Lang ◽  
Jae U. Jung

ABSTRACT Kaposi's sarcoma-associated herpesvirus encodes two highly related membrane-associated, RING-CH-containing (MARCH) family E3 ubiquitin ligases, K3 and K5, that can down regulate a variety of cell surface proteins through enhancement of their endocytosis and degradation. In this report we present data that while K5 modulation of major histocompatibility complex class I (MHC-I) closely mirrors the mechanisms used by K3, alternative molecular pathways are utilized by this E3 ligase in the down regulation of intercellular adhesion molecule 1 (ICAM-1) and B7.2. Internalization assays demonstrate that down regulation of each target can occur through increased endocytosis from the cell surface. However, mutation of a conserved tyrosine-based endocytosis motif in K5 resulted in a protein lacking the ability to direct an increased rate of MHC-I or ICAM-1 internalization but still able to down regulate B7.2 in a ubiquitin-dependent but endocytosis-independent manner. Further, mutation of two acidic clusters abolished K5-mediated MHC-I degradation while only slightly decreasing ICAM-1 or B7.2 protein destruction. This same mutant abolished detectable ubiquitylation of all targets. These data indicate that while K5 can act as an E3 ubiquitin ligase to directly mediate cell surface molecule destruction, regulation of its targets occurs through multiple pathways, including ubiquitin-independent mechanisms.


Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 666-671
Author(s):  
J Taylor ◽  
R Afrasiabi ◽  
JL Fahey ◽  
E Korns ◽  
M Weaver ◽  
...  

Sixteen immunological parameters were assessed quantitatively for their value in providing an immunologically-based and prognostically significant classification of the immune alteration in 97 patients with AIDS and Kaposi's sarcoma (AIDS-KS). The dimensions of reductions in the T4 (T helper-inducer cells) subpopulation of lymphoid cells in the T4-T8 ratio were found to correlate most closely with prognosis. Most other immunological changes did not relate to clinical course. T4 lymphocyte levels greater than 300/microL and a T4-T8 ratio greater than 0.5 indicated a relatively good prognosis, eg, 85% to 95% survival at 12 months. T4 levels less than 100/microL and/or a T4-T8 ratio less than 0.2 had a very poor prognosis, eg, less than 25% survival at 12 months. Intermediate T4 levels and T4-T8 ratios had intermediate prognosis. These immunological findings were found to have independent prognostic value for survival when compared with disease classifications based on tumor stage (I through IV) or on clinical status A (without) or B (with fever, night sweats, or weight loss). Reduced proliferative capacity, increased OKT10 antigen expression, elevated levels of serum IgA, and immune complexes also correlated with prognosis. Elevated levels of serum IgG, cellular HLA-DR expression, and skin test anergy occurred frequently in AIDS-KS but did not have prognostic significance. Variations in level of total lymphocyte, T8 (T suppressor/cytotoxic) cell, gamma FcR receptor-positive cell number, NK activity, or level of serum IgM were less common in AIDS-KS and did not correlate with prognosis.


Author(s):  
Jeanette A. M. Maier ◽  
Massimo Mariotti ◽  
Adriana Albini ◽  
Paola Comi ◽  
Maria Prat ◽  
...  

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 666-671 ◽  
Author(s):  
J Taylor ◽  
R Afrasiabi ◽  
JL Fahey ◽  
E Korns ◽  
M Weaver ◽  
...  

Abstract Sixteen immunological parameters were assessed quantitatively for their value in providing an immunologically-based and prognostically significant classification of the immune alteration in 97 patients with AIDS and Kaposi's sarcoma (AIDS-KS). The dimensions of reductions in the T4 (T helper-inducer cells) subpopulation of lymphoid cells in the T4-T8 ratio were found to correlate most closely with prognosis. Most other immunological changes did not relate to clinical course. T4 lymphocyte levels greater than 300/microL and a T4-T8 ratio greater than 0.5 indicated a relatively good prognosis, eg, 85% to 95% survival at 12 months. T4 levels less than 100/microL and/or a T4-T8 ratio less than 0.2 had a very poor prognosis, eg, less than 25% survival at 12 months. Intermediate T4 levels and T4-T8 ratios had intermediate prognosis. These immunological findings were found to have independent prognostic value for survival when compared with disease classifications based on tumor stage (I through IV) or on clinical status A (without) or B (with fever, night sweats, or weight loss). Reduced proliferative capacity, increased OKT10 antigen expression, elevated levels of serum IgA, and immune complexes also correlated with prognosis. Elevated levels of serum IgG, cellular HLA-DR expression, and skin test anergy occurred frequently in AIDS-KS but did not have prognostic significance. Variations in level of total lymphocyte, T8 (T suppressor/cytotoxic) cell, gamma FcR receptor-positive cell number, NK activity, or level of serum IgM were less common in AIDS-KS and did not correlate with prognosis.


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