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Π Π°Π±ΠΎΡ‚Π°Π΅ΠΌ вмСстС Π΄ΠΎ ΠΏΠΎΠ±Π΅Π΄Ρ‹

Π˜Π·ΡƒΡ‡Π΅Π½ΠΈΠ΅ биологичСских активностСй ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Ρ… Ρ„ΠΎΡ€ΠΌ Π±Π΅Π»ΠΊΠ° Ρ€53

Π”ΠΈΡΡΠ΅Ρ€Ρ‚Π°Ρ†ΠΈΡΠŸΠΎΠΌΠΎΡ‰ΡŒ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈΠ£Π·Π½Π°Ρ‚ΡŒ ΡΡ‚ΠΎΠΈΠΌΠΎΡΡ‚ΡŒΠΌΠΎΠ΅ΠΉ Ρ€Π°Π±ΠΎΡ‚Ρ‹

ΠŸΠΎΠ»ΡƒΡ‡Π΅Π½Ρ‹ ΠΏΠ°Π½Π΅Π»ΠΈ Π»ΠΈΠ½ΠΈΠΉ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ, ΡΠΊΡΠΏΡ€Π΅ΡΡΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… Ρ€53 ΠΏΠΎΠ΄ дСксамСтазон ΠΈΠ»ΠΈ Ρ‚Π΅Ρ‚Ρ€Π°Ρ†ΠΈΠΊΠ»ΠΈΠ½ Ρ€Π΅Π³ΡƒΠ»ΠΈΡ€ΡƒΠ΅ΠΌΡ‹ΠΌΠΈ ΠΏΡ€ΠΎΠΌΠΎΡ‚ΠΎΡ€Π°ΠΌΠΈ. Π’ ΡΡ‚ΠΈΡ… систСмах Π±Ρ‹Π»ΠΎ установлСно: Π°) БущСствуСт позитивная коррСляция ΠΌΠ΅ΠΆΠ΄Ρƒ экспрСсиСй ΠΌΡƒΡ‚Π°Π½Ρ‚Π½ΠΎΠ³ΠΎ Ρ€53 ΠΈ ΠΏΠΎΠ²Ρ‹ΡˆΠ΅Π½ΠΈΠ΅ΠΌ транскрипции ΠΎΠ±Π½Π°Ρ€ΡƒΠΆΠ΅Π½Π½Ρ‹Ρ… Π³Π΅Π½ΠΎΠ². Π±) Для Π°ΠΊΡ‚ΠΈΠ²Π°Ρ†ΠΈΠΈ Π³Π΅Π½ΠΎΠ² Π΄Π£Π’Π€Π°Π·Ρ‹, 21ΠΊΠ”, № 38 ΠΈ NAP1 ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹ΠΌΠΈ Π±Π΅Π»ΠΊΠ°ΠΌΠΈ Ρ€53 трСбуСтся Π½Π΅ΠΏΠΎΠ²Ρ€Π΅ΠΆΠ΄Π΅Π½Π½Ρ‹ΠΉ N-ΠΊΠΎΠ½Ρ†Π΅Π²ΠΎΠΉ транскрипционный Π΄ΠΎΠΌΠ΅Π½. Π²… Π§ΠΈΡ‚Π°Ρ‚ΡŒ Π΅Ρ‰Ρ‘ >

Π‘ΠΎΠ΄Π΅Ρ€ΠΆΠ°Π½ΠΈΠ΅

  • Π‘ΠΎΠ΄Π΅Ρ€ΠΆΠ°Π½ΠΈΠ΅
  • Бписок сокращСний
  • 1. ΠžΠ±Π·ΠΎΡ€ Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Ρ‹
  • Π’Π²Π΅Π΄Π΅Π½ΠΈΠ΅
    • 1. 1. ΠžΠ±Ρ‰Π°Ρ характСристика Π°Π½Ρ‚ΠΈΠΎΠ½ΠΊΠΎΠ³Π΅Π½Π° Ρ€
      • 1. 1. 1. ΠœΠΎΠ»Π΅ΠΊΡƒΠ»ΡΡ€Π½Π°Ρ организация Π³Π΅Π½Π° Ρ€
      • 1. 1. 2. ΠœΡƒΡ‚Π°Ρ†ΠΈΠΈ Π³Π΅Π½Π° Ρ€53 Π² ΠΎΠΏΡƒΡ…олях Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ°
      • 1. 1. 3. ДомСнная организация Π±Π΅Π»ΠΊΠ° Ρ€
      • 1. 1. 4. РСнтгСноструктурный Π°Π½Π°Π»ΠΈΠ· Ρ€
    • 1. 2. БиологичСскиС активности Π±Π΅Π»ΠΊΠ° Ρ€
      • 1. 2. 1. Π‘Π΅Π»ΠΎΠΊ Ρ€53 транскрипционный Π°ΠΊΡ‚ΠΈΠ²Π°Ρ‚ΠΎΡ€ ΠΈ Ρ€Π΅ΠΏΡ€Π΅ΡΡΠΎΡ€
      • 1. 2. 2. УчастиС Ρ€53 Π² Ρ€Π΅Π³ΡƒΠ»ΡΡ†ΠΈΠΈ свСрочных Ρ‚ΠΎΡ‡Π΅ΠΊ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π°
        • 1. 2. 2. 1. РСгуляция G1/S ΠΏΠ΅Ρ€Π΅Ρ…ΠΎΠ΄Π° ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π°. Π 53-зависимый Gl Π°Ρ€Π΅ΡΡ‚
        • 1. 2. 2. 2. Π 53-зависимый G2 арСст
      • 1. 2. 3. Π“Π΅Π½Ρ‹-мишСни Ρ€53 ΠΈ Ρ€53-зависимого Π°ΠΏΠΎΠΏΡ‚ΠΎΠ·Π°
      • 1. 2. 4. Π“Π΅Π½Ρ‹-мишСни Ρ€53, функция ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… Π½Π΅ Π²Ρ‹ΡΡΠ½Π΅Π½Π°
    • 1. 3. Активация ΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ транскрипционного Ρ„Π°ΠΊΡ‚ΠΎΡ€Π° — Ρ€
      • 1. 3. 1. ВзаимодСйствиС с ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹ΠΌΠΈ Π±Π΅Π»ΠΊΠ°ΠΌΠΈ Mdm2, JNK, WT1 ΠΈ ATM
      • 1. 3. 2. ΠšΠΎΠ°ΠΊΡ‚ΠΈΠ²Π°Ρ‚ΠΎΡ€Ρ‹ Ρ€
      • 1. 3. 3. ВзаимодСйствиС Ρ€53 с Π²ΠΈΡ€ΡƒΡΠ½Ρ‹ΠΌΠΈ ΠΎΠ½ΠΊΠΎΠ±Π΅Π»ΠΊΠ°ΠΌΠΈ
      • 1. 3. 4. ΠŸΠΎΡΡ‚Ρ€Π°Π½ΡΠ»ΡΡ†ΠΈΠΎΠ½Π½Ρ‹Π΅ ΠΌΠΎΠ΄ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΠΈ Ρ€53. 54 1.3.4.1. ЀосфорилированиС
        • 1. 3. 4. 2. АцСтилированиС Ρ€
    • 1. 4. БистСмы Π΄Π΅Π³Ρ€Π°Π΄Π°Ρ†ΠΈΠΈ Ρ€
    • 1. 5. БиологичСскиС активности ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Ρ… Ρ„ΠΎΡ€ΠΌ Π±Π΅Π»ΠΊΠ° Ρ€
      • 1. 5. 1. ΠšΠΎΠΎΠΏΠ΅Ρ€Π°Ρ†ΠΈΡ ΠΌΡƒΡ‚Π°Π½Ρ‚Π½ΠΎΠ³ΠΎ Π±Π΅Π»ΠΊΠ° Ρ€53 с ΠΎΠ½ΠΊΠΎΠ³Π΅Π½Π°ΠΌΠΈ
      • 1. 5. 2. УчастиС ΠΌΡƒΡ‚Π°Π½Ρ‚Π½ΠΎΠ³ΠΎ Ρ€53 Π² ΠΈΠΌΠΌΠΎΡ€Ρ‚Π°Π»ΠΈΠ·Π°Ρ†ΠΈΠΈ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ
      • 1. 5. 3. ΠŸΠΎΠ·ΠΈΡ‚ΠΈΠ²Π½Π°Ρ рСгуляция синтСза Π”ΠΠš ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹ΠΌ Π±Π΅Π»ΠΊΠΎΠΌ Ρ€
      • 1. 5. 4. ВзаимодСйствиС ΠΌΡƒΡ‚Π°Π½Ρ‚Π½ΠΎΠ³ΠΎ Ρ€53 с Π±Π΅Π»ΠΊΠ°ΠΌΠΈ Ρ‚Π΅ΠΏΠ»ΠΎΠ²ΠΎΠ³ΠΎ шока
      • 1. 5. 5. БпСцифичСскоС связываниС ΠΌΡƒΡ‚Π°Π½Ρ‚Π½ΠΎΠ³ΠΎ Ρ€53 с Ρ€ΡΠ΄ΠΎΠΌ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹Ρ… Π±Π΅Π»ΠΊΠΎΠ²
      • 1. 5. 6. ВзаимодСйствиС ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Ρ… Ρ„ΠΎΡ€ΠΌ Π±Π΅Π»ΠΊΠ° Ρ€53 с Π”ΠΠš
      • 1. 5. 7. Π₯арактСристика Ρ‚Ρ€Π°Π½ΡΠ°ΠΊΡ‚ΠΈΠ²ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… активностСй ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Ρ… Ρ„ΠΎΡ€ΠΌ Ρ€
    • 1. 6. ΠšΠΎΠ½Ρ„ΠΎΡ€ΠΌΠ°Ρ†ΠΈΠΈ ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Ρ… Ρ„ΠΎΡ€ΠΌ Π±Π΅Π»ΠΊΠ° Ρ€
    • 1. 7. ΠœΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹ΠΉ Ρ€53-Π΄ΠΎΠΌΠΈΠ½Π°Π½Ρ‚Π½Ρ‹ΠΉ ΠΈΠ»ΠΈ рСцСссивный ΠΎΠ½ΠΊΠΎΠ³Π΅Π½
    • 1. 8. Бтабилизация ΠΌΡƒΡ‚Π°Π½Ρ‚Π½ΠΎΠ³ΠΎ Π±Π΅Π»ΠΊΠ° Ρ€
    • 1. 9. БубклСточная локализация Π±Π΅Π»ΠΊΠ° Ρ€
  • 2. ΠœΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π»Ρ‹ ΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹
    • 2. 1. ΠšΡƒΠ»ΡŒΡ‚ΠΈΠ²ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹Ρ… Π»ΠΈΠ½ΠΈΠΉ
    • 2. 2. ΠŸΠΎΠ»ΡƒΡ‡Π΅Π½ΠΈΠ΅ ΠΏΠ°Π½Π΅Π»Π΅ΠΉ Π»ΠΈΠ½ΠΈΠΉ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ° ΠΈ ΠΌΡ‹ΡˆΠΈ, ΡΠΊΡΠΏΡ€Π΅ΡΡΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… Ρ€53 Π΄ΠΈΠΊΠΎΠΉ ΠΈ ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Ρ… Ρ„ΠΎΡ€ΠΌ ΠΏΠΎΠ΄ ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»Π΅ΠΌ Π³ΠΎΡ€ΠΌΠΎΠ½-зависимого ΠΈΠ»ΠΈ Ρ‚Π΅Ρ‚Ρ€Π°Ρ†ΠΈΠΊΠ»ΠΈΠ½-Ρ€Π΅Π³ΡƒΠ»ΠΈΡ€ΡƒΠ΅ΠΌΠΎΠ³ΠΎ ΠΏΡ€ΠΎΠΌΠΎΡ‚ΠΎΡ€Π°
    • 2. 3. Π˜ΠΌΠΌΡƒΠ½ΠΎΠΏΡ€Π΅Ρ†ΠΈΠΏΠΈΡ‚Π°Ρ†ΠΈΡ
    • 2. 4. Π€Ρ€Π°ΠΊΡ†ΠΈΠΎΠ½ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠΎΠ² Π² ΠΏΠΎΠ»ΠΈΠ°ΠΊΡ€ΠΈΠ»Π°ΠΌΠΈΠ΄Π½ΠΎΠΌ Π³Π΅Π»Π΅
    • 2. 5. ΠŸΠ΅Ρ€Π΅Π½ΠΎΡ Π±Π΅Π»ΠΊΠΎΠ² ΠΈΠ· Π³Π΅Π»Π΅ΠΉ Π½Π° Π½ΠΈΡ‚Ρ€ΠΎΡ†Π΅Π»Π»ΡŽΠ»ΠΎΠ·Π½Ρ‹Π΅ Ρ„ΠΈΠ»ΡŒΡ‚Ρ€Ρ‹ ΠΈ ΠΈΠΌΠΌΡƒΠ½ΠΎΠ΄Π΅Ρ‚Скция Ρ€
    • 2. 6. Π‘Π°ΠΊΡ‚Π΅Ρ€ΠΈΠ°Π»ΡŒΠ½Ρ‹Π΅ ΡˆΡ‚Π°ΠΌΠΌΡ‹, ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Ρ‹, рСтровирусныС Π²Π΅ΠΊΡ‚ΠΎΡ€Π°
    • 2. 7. ΠŸΠΎΠ»ΡƒΡ‡Π΅Π½ΠΈΠ΅ ΠΊΠΎΠΌΠΏΠ΅Ρ‚Π΅Π½Ρ‚Π½Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ DH
    • 2. 8. Π’Ρ‹Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Π½ΠΎΠΉ Π”ΠΠš
      • 2. 8. 1. ΠŸΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ΠΈΠ²Π½ΠΎΠ΅ Π²Ρ‹Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Π½ΠΎΠΉ Π”ΠΠš
      • 2. 8. 2. АналитичСскоС Π²Ρ‹Π΄Π΅Π»Π΅Π½ΠΈΠ΅ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Π½ΠΎΠΉ Π”ΠΠš
    • 2. 9. ΠžΠ±Ρ€Π°Π±ΠΎΡ‚ΠΊΠ° Π”ΠΠš рСстрикционными эндонуклСазами
    • 2. 10. Π€Ρ€Π°ΠΊΡ†ΠΈΠΎΠ½ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Π”ΠΠš Π² Π°Π³Π°Ρ€ΠΎΠ·Π½Ρ‹Ρ… гСлях
    • 2. 11. Π˜Π·Π²Π»Π΅Ρ‡Π΅Π½ΠΈΠ΅ Π”ΠΠš ΠΈΠ· Π°Π³Π°Ρ€ΠΎΠ·Π½Ρ‹Ρ… Π³Π΅Π»Π΅ΠΉ
    • 2. 12. Π‘ΡƒΠ±ΠΊΠ»ΠΎΠ½ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚ΠΎΠ² Π”ΠΠš Π² Π²Π΅ΠΊΡ‚ΠΎΡ€Π° pPS-neo, pSIT-neo, pMMTV
      • 2. 12. 1. ΠŸΠΎΠ»ΡƒΡ‡Π΅Π½ΠΈΠ΅ Π²Π΅ΠΊΡ‚ΠΎΡ€Π½ΠΎΠΉ Π”ΠΠš
      • 2. 12. 2. РСакция лигирования
    • 2. 13. Врансформация ΠΊΠΎΠΌΠΏΠ΅Ρ‚Π΅Π½Ρ‚Π½Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ E. Coli ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Π½ΠΎΠΉ Π”ΠΠš
    • 2. 14. ВрансфСкция рСтровирусных ΠΈ ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Π½Ρ‹Ρ… конструктов ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ ΠΊΠ°Π»ΡŒΡ†ΠΈΠΉ-фосфатной ΠΏΡ€Π΅Ρ†ΠΈΠΏΠΈΡ‚Π°Ρ†ΠΈΠΈ
    • 2. 15. ΠžΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ эффСктивности трансфСкции ΠΈ ΠΈΠ½Ρ„Π΅ΠΊΡ†ΠΈΠΈ ΠΏΠΎ Ρ„Π»ΡŽΠΎΡ€ΠΈΡΡ†Π΅Π½Ρ†ΠΈΠΈ Π·Π΅Π»Π΅Π½ΠΎΠ³ΠΎ Π±Π΅Π»ΠΊΠ°
    • 2. 16. Π˜Π½Ρ„Π΅ΠΊΡ†ΠΈΡ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Ρ€Π΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½Ρ‚Π½Ρ‹ΠΌΠΈ рСтровирусами
    • 2. 17. ΠŸΠΎΠ»ΠΈΠΌΠ΅Ρ€Π°Π·Π½Π°Ρ цСпная рСакция (ПЦР)
    • 2. 18. ΠžΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π½ΡƒΠΊΠ»Π΅ΠΎΡ‚ΠΈΠ΄Π½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΠΈ ΠΏΠΎ ΠΌΠ΅Ρ‚ΠΎΠ΄Ρƒ БэнгСра. 86 2.19 Экстракция РНК ΠΈ Nothern-Π±Π»ΠΎΡ‚Ρ‚ΠΈΠ½Π³. ?6−87 2.20. ΠœΠ΅Ρ‚ΠΎΠ΄ субтрактивной Π³ΠΈΠ±Ρ€ΠΈΠ΄ΠΈΠ·Π°Ρ†ΠΈΠΈ
    • 2. 21. Π’Ρ‹Π΄Π΅Π»Π΅Π½ΠΈΠ΅ высокомолСкулярной Π”ΠΠš
    • 2. 22. Гибридизация ΠΏΠΎ Π‘Π°ΡƒΠ·Π΅Ρ€Π½Ρƒ
    • 2. 23. Анализ активности Ρ…Π»ΠΎΡ€Π°ΠΌΡ„Π΅Π½ΠΈΠΊΠΎΠ»-ацСтилтрансфСразы (БАВ-рСакция)
    • 2. 24. ΠŸΡ€ΠΎΡΡ‡Π΅Ρ‚ радиоактивности Π² ΠΏΡ€ΠΎΠ±Π°Ρ…
    • 2. 25. Авторадиография
    • 2. 26. ΠšΠΎΠΌΠΏΡŒΡŽΡ‚Π΅Ρ€Π½Ρ‹ΠΉ Π°Π½Π°Π»ΠΈΠ·
  • 3. Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ ΠΈ ΠΈΡ… ΠΎΠ±ΡΡƒΠΆΠ΄Π΅Π½ΠΈΠ΅
  • 1. Π 53 с ΠΌΡƒΡ‚Π°Ρ†ΠΈΠ΅ΠΉ Π² ΠΊΠΎΠ΄ΠΎΠ½Π΅ 273 ΡƒΠ²Π΅Π»ΠΈΡ‡ΠΈΠ²Π°Π΅Ρ‚ Π²Π΅Ρ€ΠΎΡΡ‚Π½ΠΎΡΡ‚ΡŒ Π°ΠΌΠΏΠ»ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΠΈ Π³Π΅Π½Π° с1Мг
  • 2. ИсслСдованиС трансактивационных свойств ΠΌΡƒΡ‚Π°Π½Ρ‚ΠΎΠ² Ρ€
  • 3. Π˜Π΄Π΅Π½Ρ‚ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΡ Π³Π΅Π½ΠΎΠ², Π°ΠΊΡ‚ΠΈΠ²ΠΈΡ€ΡƒΠ΅ΠΌΡ‹Ρ… ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹ΠΌΠΈ Ρ„ΠΎΡ€ΠΌΠ°ΠΌΠΈ Ρ€
  • 4. ΠŸΠΎΠ»ΡƒΡ‡Π΅Π½ΠΈΠ΅ ΠΏΠΎΠ»Π½ΠΎΡ€Π°Π·ΠΌΠ΅Ρ€Π½Ρ‹Ρ… ΠΊΠ”ΠΠš Π³Π΅Π½ΠΎΠ² Π΄Π£Π’Π€Π°Π·Ρ‹, N038 ΠΈ 21Π¨Π° ΠΌΡ‹ΡˆΠΈ
  • 5. Анализ экспрСссии Π³Π΅Π½ΠΎΠ² Π΄Π£Π’Π€Π°Π·Ρ‹, N038, 21Π¨Π° ΠΈ NAP1 Π² ΠΏΠ΅Ρ€Π΅Π²ΠΈΠ²Π°Π΅ΠΌΡ‹Ρ… линиях ΠΊΠ»Π΅Ρ‚ΠΎΠΊ ΠΌΡ‹ΡˆΠΈ ΠΈ Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ°, содСрТащих Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Π΅ Ρ„ΠΎΡ€ΠΌΡ‹ Π±Π΅Π»ΠΊΠ° Ρ€
  • 6. ΠŸΠΎΠ»ΡƒΡ‡Π΅Π½ΠΈΠ΅ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ 10(3), содСрТащих дСксамСтозон-ΠΈΠ½Π΄ΡƒΡ†ΠΈΠ±Π΅Π»ΡŒΠ½Ρ‹ΠΉ Ρ€53-Π™8175, ΠΈ Π°Π½Π°Π»ΠΈΠ· экспрСссии Π³Π΅Π½ΠΎΠ² Π΄Π£Π’Π€Π°Π·Ρ‹ ΠΈ NAP1 Π² Π΄Π°Π½Π½ΠΎΠΉ систСмС
  • 7. ΠšΠΎΠ½ΡΡ‚Ρ€ΡƒΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Π»ΠΈΠ½ΠΈΠΉ 10(1), МОА-041, Н1299, Π‘Π‘-ОУ-Π— ΡΠΊΡΠΏΡ€Π΅ΡΡΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… Ρ‚Π΅Ρ‚Ρ€Π°Ρ†ΠΈΠΊΠ»ΠΈΠ½-Ρ€Π΅Π³ΡƒΠ»ΠΈΡ€ΡƒΠ΅ΠΌΡ‹ΠΉ 53 ΠΈ Π°Π½Π°Π»ΠΈΠ· экспрСссии Π³Π΅Π½ΠΎΠ² Π΄Π£Π’Π€Π°Π·Ρ‹ ΠΈ 21Π¨Π° Π² Π΄Π°Π½Π½ΠΎΠΉ систСмС
  • 8. ВлияниС экспрСсии ΠΌΡƒΡ‚Π°Π½Ρ‚Π½ΠΎΠ³ΠΎ Ρ€53И$ 175 Π½Π° ΡƒΡΡ‚ΠΎΠΉΡ‡ΠΈΠ²ΠΎΡΡ‚ΡŒ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ
  • 10. (1) ΠΊ 5-Ρ„Ρ‚ΠΎΡ€-ΡƒΡ€ΠΈΠ΄ΠΈΠ½Ρƒ
  • 4. Π’Ρ‹Π²ΠΎΠ΄Ρ‹

Π˜Π·ΡƒΡ‡Π΅Π½ΠΈΠ΅ биологичСских активностСй ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Ρ… Ρ„ΠΎΡ€ΠΌ Π±Π΅Π»ΠΊΠ° Ρ€53 (Ρ€Π΅Ρ„Π΅Ρ€Π°Ρ‚, курсовая, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒΠ½Π°Ρ)

ΠžΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹ΠΉ супрСссор Ρ€53 ΠΈΠ³Ρ€Π°Π΅Ρ‚ Π²Π°ΠΆΠ½ΡƒΡŽ ΠΎΡ…Ρ€Π°Π½Π½ΡƒΡŽ Ρ€ΠΎΠ»ΡŒ, прСдотвращая Ρ€Π°Π·ΠΌΠ½ΠΎΠΆΠ΅Π½ΠΈΠ΅ ΠΈ Π½Π°ΠΊΠΎΠΏΠ»Π΅Π½ΠΈΠ΅ Π² ΠΎΡ€Π³Π°Π½ΠΈΠ·ΠΌΠ΅ Π°Π½ΠΎΠΌΠ°Π»ΡŒΠ½Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ. Π’ ΠΎΡΠ½ΠΎΠ²Π΅ Ρ‚Π°ΠΊΠΎΠΉ Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΈ Ρ€53 Π»Π΅ΠΆΠΈΡ‚ Π΅Π³ΠΎ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡ‚ΡŒ Π°ΠΊΡ‚ΠΈΠ²ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒΡΡ ΠΏΡ€ΠΈ самых Ρ€Π°Π·Π½Ρ‹Ρ… Π²Π½ΡƒΡ‚Ρ€ΠΈΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹Ρ… Π½Π°Ρ€ΡƒΡˆΠ΅Π½ΠΈΡΡ… ΠΈ Π²Ρ‹Π·Ρ‹Π²Π°Ρ‚ΡŒ Π² ΠΎΡ‚Π²Π΅Ρ‚ Π½Π° Π½ΠΈΡ… Π»ΠΈΠ±ΠΎ ΡΠΊΡΡ‚Ρ€Π΅Π½Π½ΡƒΡŽ остановку ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π° Π² G1 ΠΈ G2 Ρ„Π°Π·Π°Ρ…, Π»ΠΈΠ±ΠΎ Π°ΠΏΠΎΠΏΡ‚ΠΎΠ·. Активация Ρ€53 Π½Π°Π±Π»ΡŽΠ΄Π°Π΅Ρ‚ΡΡ ΠΏΡ€ΠΈ Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… Π”ΠΠš-ΠΏΠΎΠ²Ρ€Π΅ΠΆΠ΄Π°ΡŽΡ‰ΠΈΡ… воздСйствиях (Π£Π€ΠΈ Ρƒ-ΠΎΠ±Π»ΡƒΡ‡Π΅Π½ΠΈΠ΅, химичСскиС ΠΌΡƒΡ‚Π°Π³Π΅Π½Ρ‹) — ΠΏΠΎΠ½ΠΈΠΆΠ΅Π½ΠΈΠΈ Π²Π½ΡƒΡ‚Ρ€ΠΈΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ ΠΏΡƒΠ»Π° Π½ΡƒΠΊΠ»Π΅ΠΎΡ‚ΠΈΠ΄ΠΎΠ²ΠΈΠ½Π³ΠΈΠ±ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠΈ Π”ΠΠšΠΈ РНК-ΠΏΠΎΠ»ΠΈΠΌΠ΅Ρ€Π°Π· ΠΈ Π΄Ρ€ΡƒΠ³ΠΈΡ… стрСссов. Являясь спСцифичСским транскрипционным Ρ„Π°ΠΊΡ‚ΠΎΡ€ΠΎΠΌ Ρ€53 выполняСт Ρ‡Π°ΡΡ‚ΡŒ своих супрСссорных Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΉ Π·Π° ΡΡ‡Π΅Ρ‚ трансактивации Π³Π΅Π½ΠΎΠ²-мишСнСй, содСрТащих спСцифичСскиС Ρ€53 рСспонсивныС элСмСнты. НаиболСС Π·Π½Π°Ρ‡ΠΈΡ‚Π΅Π»ΡŒΠ½ΡƒΡŽ Ρ€ΠΎΠ»ΡŒ Π² Π·Π°Π΄Π΅Ρ€ΠΆΠΊΠ΅ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π° ΠΈΠ³Ρ€Π°Π΅Ρ‚ Ρ€53-рСспонсивный Π³Π΅Π½ p21/WAF, ΠΏΡ€ΠΎΠ΄ΡƒΠΊΡ‚ ΠΊΠΎΡ‚ΠΎΡ€ΠΎΠ³ΠΎ являСтся ΡƒΠ½ΠΈΠ²Π΅Ρ€ΡΠ°Π»ΡŒΠ½Ρ‹ΠΌ ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€ΠΎΠΌ Ρ†ΠΈΠΊΠ»ΠΈΠ½-зависимых ΠΊΠΈΠ½Π°Π·. ΠŸΠΎΠ²Ρ‹ΡˆΠ΅Π½ΠΈΠ΅ экспрСссии p21/WAF Π²Ρ‹Π·Ρ‹Π²Π°Π΅Ρ‚ остановку ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π° Π² G1 ΠΈ G2 Ρ„Π°Π·Π°Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π°. Π‘Π»ΠΎΠΊΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΠΎΠ²Ρ€Π΅ΠΆΠ΄Π΅Π½Π½Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Π² G2 связано, вСроятно, Ρ‚Π°ΠΊΠΆΠ΅ с Π°ΠΊΡ‚ΠΈΠ²Π°Ρ†ΠΈΠ΅ΠΉ ΠΈ Π΄Ρ€ΡƒΠ³ΠΎΠ³ΠΎ Ρ€53-рСспонсивного Π³Π΅Π½Π° — gadd45. Π˜Π½Π΄ΡƒΠΊΡ†ΠΈΡ Ρ€53-зависимого Π°ΠΏΠΎΠΏΡ‚ΠΎΠ·Π° обусловливаСтся, ΠΏΠΎ-Π²ΠΈΠ΄ΠΈΠΌΠΎΠΌΡƒ, Π°ΠΊΡ‚ΠΈΠ²Π°Ρ†ΠΈΠ΅ΠΉ Π³Π΅Π½Π° проапоптотичСского Π±Π΅Π»ΠΊΠ° Π’ Π°Ρ…, Π° Ρ‚Π°ΠΊΠΆΠ΅ ряда Π΄Ρ€ΡƒΠ³ΠΈΡ… Π³Π΅Π½ΠΎΠ², ΠΏΡ€ΠΎΠ΄ΡƒΠΊΡ‚Ρ‹ ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… ΡΡ‚ΠΈΠΌΡƒΠ»ΠΈΡ€ΡƒΡŽΡ‚ Π°ΠΏΠΎΠΏΡ‚ΠΎΠ· — Fas, KILLER/DR5, Π³Ρ€ΡƒΠΏΠΏΠ° Π³Π΅Π½ΠΎΠ² PIG ΠΈ Ρ‚. Π΄.

ΠΠ°Ρ€ΡƒΡˆΠ΅Π½ΠΈΡ Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΈ Π³Π΅Π½Π° Ρ€53 приводят ΠΊ ΠΈΠ½Π°ΠΊΡ‚ΠΈΠ²Π°Ρ†ΠΈΠΈ «ΡΠ²Π΅Ρ€ΠΎΡ‡Π½Ρ‹Ρ… Ρ‚ΠΎΡ‡Π΅ΠΊ» (checkpoints) Π² G1 ΠΈ G2 Ρ„Π°Π·Π°Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π°, ΡƒΠ²Π΅Π»ΠΈΡ‡Π΅Π½ΠΈΡŽ ТизнСспособности ΠΏΠΎΠ²Ρ€Π΅ΠΆΠ΄Π΅Π½Π½Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ ΠΈ, ΠΊΠ°ΠΊ слСдствиС, Π·Π½Π°Ρ‡ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠΌΡƒ ΡƒΠ²Π΅Π»ΠΈΡ‡Π΅Π½ΠΈΡŽ скорости накоплСния Π² ΠΎΡ€Π³Π°Π½ΠΈΠ·ΠΌΠ΅ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ с Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹ΠΌΠΈ измСнСниями Π³Π΅Π½ΠΎΠΌΠ°, Π² Ρ‚ΠΎΠΌ числС ΠΈ ΠΎΠ½ΠΊΠΎΠ³Π΅Π½Π½Ρ‹ΠΌΠΈ. Π’ Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Π΅ ΠΎΡ‚Π±ΠΎΡ€Π° ΠΈΠ· Ρ‚Π°ΠΊΠΈΡ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ ΠΎΠ±Ρ€Π°Π·ΡƒΡŽΡ‚ΡΡ ΠΎΠΏΡƒΡ…ΠΎΠ»ΠΈ. О ΠΊΠ»ΡŽΡ‡Π΅Π²ΠΎΠΉ Ρ€ΠΎΠ»ΠΈ Π½Π°Ρ€ΡƒΡˆΠ΅Π½ΠΈΠΉ Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΈ Ρ€53 Π² ΠΏΡ€ΠΎΡ†Π΅ΡΡΠ°Ρ… ΠΊΠ°Π½Ρ†Π΅Ρ€ΠΎΠ³Π΅Π½Π΅Π·Π° ΡΠ²ΠΈΠ΄Π΅Ρ‚Π΅Π»ΡŒΡΡ‚Π²ΡƒΠ΅Ρ‚ Ρ‚ΠΎΡ‚ Ρ„Π°ΠΊΡ‚, Ρ‡Ρ‚ΠΎ ΠΏΡ€ΠΈΠΌΠ΅Ρ€Π½ΠΎ Π² ΠΏΠΎΠ»ΠΎΠ²ΠΈΠ½Π΅ всСх ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅ΠΉ Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ° ΠΎΠ±Π½Π°Ρ€ΡƒΠΆΠΈΠ²Π°ΡŽΡ‚ΡΡ ΠΌΡƒΡ‚Π°Ρ†ΠΈΠΈ Π³Π΅Π½Π° Ρ€53. ΠŸΡ€ΠΈ этом, Π² ΠΎΡ‚Π»ΠΈΡ‡ΠΈΠ΅ ΠΎΡ‚ Π΄Ρ€ΡƒΠ³ΠΈΡ… ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… супрСссоров, для ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… Ρ…Π°Ρ€Π°ΠΊΡ‚Π΅Ρ€Π½Ρ‹ ΠΌΡƒΡ‚Π°Ρ†ΠΈΠΈ, ΠΏΡ€Π΅ΠΊΡ€Π°Ρ‰Π°ΡŽΡ‰ΠΈΠ΅ синтСз Π±Π΅Π»ΠΊΠ° (Π΄Π΅Π»Π΅Ρ†ΠΈΠΈ, ΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ стоп-ΠΊΠΎΠ΄ΠΎΠ½ΠΎΠ², сдвиг ΠΊΠΎΠ΄ΠΈΡ€ΡƒΡŽΡ‰Π΅ΠΉ Ρ€Π°ΠΌΠΊΠΈ, Π½Π°Ρ€ΡƒΡˆΠ΅Π½ΠΈΡ сплайсинга мРНК), ΠΏΠΎΠ΄Π°Π²Π»ΡΡŽΡ‰Π΅Π΅ Π±ΠΎΠ»ΡŒΡˆΠΈΠ½ΡΡ‚Π²ΠΎ ΠΌΡƒΡ‚Π°Ρ†ΠΈΠΉ Ρ€53 прСдставляСт собой миссСнс-ΠΌΡƒΡ‚Π°Ρ†ΠΈΠΈ, приводящиС ΠΊ Π·Π°ΠΌΠ΅Π½Π΅ ΠΎΠ΄Π½ΠΎΠΉ ΠΈΠ· Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡ‚ Π½Π° Π΄Ρ€ΡƒΠ³ΡƒΡŽ. ΠŸΡ€ΠΈΠΌΠ΅Ρ‡Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎ Ρ‚Π°ΠΊΠΆΠ΅, Ρ‡Ρ‚ΠΎ ΠΎΠΏΡƒΡ…ΠΎΠ»ΠΈ Π² ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… экспрСссируСтся ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹ΠΉ Ρ€53 Π±ΠΎΠ»Π΅Π΅ агрСссивны ΠΈ Ρ‚Ρ€ΡƒΠ΄Π½Π΅Π΅ ΠΏΠΎΠ΄Π΄Π°ΡŽΡ‚ΡΡ Π»Π΅Ρ‡Π΅Π½ΠΈΡŽ, Ρ‡Π΅ΠΌ Ρ‚Π΅, Π² ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… Π³Π΅Π½ Ρ€53 ΠΏΠΎΠ»Π½ΠΎΡΡ‚ΡŒΡŽ Π΄Π΅Π»Π΅Π³ΠΈΡ€ΠΎΠ²Π°Π½. Π‘ΠΎΠ»Π΅Π΅ Ρ‚ΠΎΠ³ΠΎ, Π±Ρ‹Π»ΠΎ ΠΎΠ±Π½Π°Ρ€ΡƒΠΆΠ΅Π½ΠΎ, Ρ‡Ρ‚ΠΎ трансдукция Π½Π΅ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Ρ… Ρ€53 Π² ΠΊΠ»Π΅Ρ‚ΠΊΠΈ, Π½Π΅ ΠΏΡ€ΠΎΠ΄ΡƒΡ†ΠΈΡ€ΡƒΡŽΡ‰ΠΈΠ΅ эндогСнный Ρ€53, ΡƒΠ²Π΅Π»ΠΈΡ‡ΠΈΠ²Π°Π΅Ρ‚ Π²Ρ‹Ρ€Π°ΠΆΠ΅Π½Π½ΠΎΡΡ‚ΡŒ Π² Π½ΠΈΡ… ΠΏΡ€ΠΈΠ·Π½Π°ΠΊΠΎΠ² трансформированного Ρ„Π΅Π½ΠΎΡ‚ΠΈΠΏΠ° in vitro ΠΈ ΠΎΠ½ΠΊΠΎΠ³Π΅Π½Π½Ρ‹ΠΉ ΠΏΠΎΡ‚Π΅Π½Ρ†ΠΈΠ°Π» in vivo. ВсС эти наблюдСния ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΠ»ΠΈ ΠΏΡ€Π΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡ‚ΡŒ, Ρ‡Ρ‚ΠΎ ΠΏΠΎ ΠΊΡ€Π°ΠΉΠ½Π΅ΠΉ ΠΌΠ΅Ρ€Π΅ Π½Π΅ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Π΅ ΠΈΠ· Π½Π°Π±Π»ΡŽΠ΄Π°ΡŽΡ‰ΠΈΡ…ся Π² ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… ΠΌΡƒΡ‚Π°Ρ†ΠΈΠΉ Π²Ρ‹Π·Ρ‹Π²Π°ΡŽΡ‚ Π½Π΅ Ρ‚ΠΎΠ»ΡŒΠΊΠΎ ΠΈΠ½Π°ΠΊΡ‚ΠΈΠ²Π°Ρ†ΠΈΡŽ супрСссорных активностСй Ρ€53, Π½ΠΎ ΠΈ ΠΏΡ€ΠΈΠ΄Π°ΡŽΡ‚ Π΅ΠΌΡƒ ряд Π½ΠΎΠ²Ρ‹Ρ… активностСй, нСсвойствСнных Π±Π΅Π»ΠΊΡƒ Π΄ΠΈΠΊΠΎΠ³ΠΎ Ρ‚ΠΈΠΏΠ°.

ΠŸΡ€Π΅Π΄ΠΏΠΎΠ»Π°Π³Π°Π΅Ρ‚ΡΡ, Ρ‡Ρ‚ΠΎ Π½ΠΎΠ²Ρ‹Π΅ активности ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Ρ… Ρ€53 Π·Π°ΠΊΠ»ΡŽΡ‡Π°ΡŽΡ‚ΡΡ, ΠΏΡ€Π΅ΠΆΠ΄Π΅ всСго, Π² ΠΏΡ€ΠΈΠΎΠ±Ρ€Π΅Ρ‚Π΅Π½ΠΈΠΈ способности ΡƒΠ²Π΅Π»ΠΈΡ‡ΠΈΠ²Π°Ρ‚ΡŒ ΡΠΊΡΠΏΡ€Π΅ΡΡΠΈΡŽ Π³Π΅Π½ΠΎΠ², Π½Π΅ ΡΠ²Π»ΡΡŽΡ‰ΠΈΡ…ся транскрипционными мишСнями Π±Π΅Π»ΠΊΠ° Π΄ΠΈΠΊΠΎΠ³ΠΎ Ρ‚ΠΈΠΏΠ°. Π’Π°ΠΊ, Π±Ρ‹Π»ΠΎ продСмонстрировано, Ρ‡Ρ‚ΠΎ ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Π΅ Ρ€53 с Π·Π°ΠΌΠ΅Π½Π°ΠΌΠΈ Π² ΠΊΠΎ Π΄ΠΎΠ½Π°Ρ… 175, 273 ΠΈ 282 способны, Π² ΠΎΡ‚Π»ΠΈΡ‡ΠΈΠ΅ ΠΎΡ‚ p53-wt, Π°ΠΊΡ‚ΠΈΠ²ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ ΠΏΡ€ΠΎΠΌΠΎΡ‚ΠΎΡ€Ρ‹ Π³Π΅Π½ΠΎΠ² MDR1, PCNA, c-myc, hEGFR, VEGF, hIL-6, BFGF ΠΈ hHSP70. Однако, этот список Π½Π΅ ΠΈΡΡ‡Π΅Ρ€ΠΏΡ‹Π²Π°Π΅Ρ‚, ΠΎΡ‡Π΅Π²ΠΈΠ΄Π½ΠΎ, спСктр Π³Π΅Π½ΠΎΠ², Π°ΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒ ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… модифицируСтся ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹ΠΌΠΈ Ρ€53. Π˜Π΄Π΅Π½Ρ‚ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΡ нСизвСстных Ρ€Π°Π½Π΅Π΅ мишСнСй ΠΈΡ… Ρ‚ранскрипционных активностСй ΠΌΠΎΠΆΠ΅Ρ‚ ΠΎΠΊΠ°Π·Π°Ρ‚ΡŒΡΡ вСсьма Π²Π°ΠΆΠ½ΠΎΠΉ для Π±ΠΎΠ»Π΅Π΅ ΠΏΠΎΠ»Π½ΠΎΠ³ΠΎ понимания Ρ€ΠΎΠ»ΠΈ ΠΌΡƒΡ‚Π°Ρ†ΠΈΠΉ Ρ€53 Π² ΠΏΡ€ΠΎΡ†Π΅ΡΡΠ°Ρ… ΠΊΠ°Π½Ρ†Π΅Ρ€ΠΎΠ³Π΅Π½Π΅Π·Π°.

Π²Ρ‹Π²ΠΎΠ΄Ρ‹.

1. УстановлСно, Ρ‡Ρ‚ΠΎ Ρ€53 с ΠΌΡƒΡ‚Π°Ρ†ΠΈΠ΅ΠΉ Π² ΠΊΠΎΠ΄ΠΎΠ½Π΅ 273 ΡƒΠ²Π΅Π»ΠΈΡ‡ΠΈΠ²Π°Π΅Ρ‚ частоту Π°ΠΌΠΏΠ»ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΠΈ Π³Π΅Π½Π° DHFR. Π’Π°ΠΊΠΈΠΌ ΠΎΠ±Ρ€Π°Π·ΠΎΠΌ ΠΈΠ΄Π΅Π½Ρ‚ΠΈΡ„ΠΈΡ†ΠΈΡ€ΠΎΠ²Π°Π½Π° Π΅Ρ‰Π΅ ΠΎΠ΄Π½Π° Π°ΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒ ΠΌΡƒΡ‚Π°Π½Ρ‚Π½ΠΎΠ³ΠΎ Ρ€53, способная Π΄Π΅ΡΡ‚Π°Π±ΠΈΠ»ΠΈΠ·ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ Π³Π΅Π½ΠΎΠΌ ΠΊΠ»Π΅Ρ‚ΠΊΠΈ ΠΈ ΡƒΡΠΊΠΎΡ€ΡΡ‚ΡŒ процСссы ΠΊΠ°Π½Ρ†Π΅Ρ€ΠΎΠ³Π΅Π½Π΅Π·Π°.

2. Показано, Ρ‡Ρ‚ΠΎ ΠΌΡƒΡ‚Π°Π½Ρ‚Ρ‹ Ρ€53 (Hisl75, Trp248, His273) Π½Π΅ ΡΠΏΠΎΡΠΎΠ±Π½Ρ‹ Π°ΠΊΡ‚ΠΈΠ²ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ Ρ‚Ρ€Π°Π½ΡΠΊΡ€ΠΈΠΏΡ†ΠΈΡŽ с ΠΏΡ€ΠΎΠΌΠΎΡ‚ΠΎΡ€ΠΎΠ², содСрТащих ряд Ρ€53-рСспонсивных элСмСнтов. ΠŸΠΎΡΡ‚ΠΎΠΌΡƒ каТСтся маловСроятным, Ρ‡Ρ‚ΠΎ Π² ΠΎΡΠ½ΠΎΠ²Π΅ появлСния Π½ΠΎΠ²Ρ‹Ρ… активностСй ΠΌΡƒΡ‚Π°Π½Ρ‚Π½ΠΎΠ³ΠΎ Ρ€53 Π»Π΅ΠΆΠΈΡ‚ активация ΠΎΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½Π½ΠΎΠ³ΠΎ ΠΏΠΎΠ΄Π½Π°Π±ΠΎΡ€Π° Ρ€53-рСспонсивных элСмСнтов.

3. ΠžΠ±Π½Π°Ρ€ΡƒΠΆΠ΅Π½Ρ‹ Ρ‡Π΅Ρ‚Ρ‹Ρ€Π΅ Π½ΠΎΠ²Ρ‹Ρ… эндогСнных мишСни ΠΌΡƒΡ‚Π°Π½Ρ‚ΠΎΠ³ΠΎ Π±Π΅Π»ΠΊΠ° Ρ€53 -это Π³Π΅Π½Ρ‹ Π΄Π£Π’Π€Π°Π·Ρ‹, 21ΠΊΠ”, N038, ΠΈ NAP1. Показана гипСрэкспрСссия Π΄Π°Π½Π½Ρ‹Ρ… Π³Π΅Π½ΠΎΠ² Π² Ρ€ΡΠ΄Π΅ Π»ΠΈΠ½ΠΈΠΉ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ ΠΌΡ‹ΡˆΠΈ ΠΈ Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ°, ΡΠΊΡΠΏΡ€Π΅ΡΡΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Π΅ Ρ„ΠΎΡ€ΠΌΡ‹ Ρ€53.

4. ΠŸΠΎΠ»ΡƒΡ‡Π΅Π½Ρ‹ ΠΏΠ°Π½Π΅Π»ΠΈ Π»ΠΈΠ½ΠΈΠΉ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ, ΡΠΊΡΠΏΡ€Π΅ΡΡΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… Ρ€53 ΠΏΠΎΠ΄ дСксамСтазон ΠΈΠ»ΠΈ Ρ‚Π΅Ρ‚Ρ€Π°Ρ†ΠΈΠΊΠ»ΠΈΠ½ Ρ€Π΅Π³ΡƒΠ»ΠΈΡ€ΡƒΠ΅ΠΌΡ‹ΠΌΠΈ ΠΏΡ€ΠΎΠΌΠΎΡ‚ΠΎΡ€Π°ΠΌΠΈ. Π’ ΡΡ‚ΠΈΡ… систСмах Π±Ρ‹Π»ΠΎ установлСно: Π°) БущСствуСт позитивная коррСляция ΠΌΠ΅ΠΆΠ΄Ρƒ экспрСсиСй ΠΌΡƒΡ‚Π°Π½Ρ‚Π½ΠΎΠ³ΠΎ Ρ€53 ΠΈ ΠΏΠΎΠ²Ρ‹ΡˆΠ΅Π½ΠΈΠ΅ΠΌ транскрипции ΠΎΠ±Π½Π°Ρ€ΡƒΠΆΠ΅Π½Π½Ρ‹Ρ… Π³Π΅Π½ΠΎΠ². Π±) Для Π°ΠΊΡ‚ΠΈΠ²Π°Ρ†ΠΈΠΈ Π³Π΅Π½ΠΎΠ² Π΄Π£Π’Π€Π°Π·Ρ‹, 21ΠΊΠ”, № 38 ΠΈ NAP1 ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹ΠΌΠΈ Π±Π΅Π»ΠΊΠ°ΠΌΠΈ Ρ€53 трСбуСтся Π½Π΅ΠΏΠΎΠ²Ρ€Π΅ΠΆΠ΄Π΅Π½Π½Ρ‹ΠΉ N-ΠΊΠΎΠ½Ρ†Π΅Π²ΠΎΠΉ транскрипционный Π΄ΠΎΠΌΠ΅Π½. Π²) Π˜Π½Π΄ΡƒΠΊΡ†ΠΈΡ синтСза Π±Π΅Π»ΠΊΠ° p53Hisl75 ΠΏΡ€ΠΈΠ²ΠΎΠ΄ΠΈΡ‚ ΠΊ ΠΏΠΎΠ²Ρ‹ΡˆΠ΅Π½ΠΈΡŽ устойчивости ΠΊΠ»Π΅Ρ‚ΠΎΠΊ ΠΊ ΠΎΠ±Ρ€Π°Π±ΠΎΡ‚ΠΊΠ΅ Ρ„Ρ‚ΠΎΡ€-дСзоксиуридином. Π’Π°ΠΊΠΎΠΉ ΠΆΠ΅ эффСкт сопровоТдаСт Π³ΠΈΠΏΠ΅Ρ€ΡΠΊΡΠΏΡ€Π΅ΡΡΠΈΡŽ дСзокси-Π£Π’Π€Π°Π·Ρ‹. Ѐункция выявлСнных Π½Π°ΠΌΠΈ Π³Π΅Π½ΠΎΠ² ΠΌΠΎΠΆΠ΅Ρ‚ ΠΎΠ±ΡŠΡΡΠ½ΠΈΡ‚ΡŒ ΠΏΠΎ ΠΊΡ€Π°ΠΉΠ½Π΅ΠΉ ΠΌΠ΅Ρ€Π΅ Ρ‡Π°ΡΡ‚ΡŒ биологичСских активностСй ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Ρ… Ρ€53.

5. Π’Ρ‹Π΄Π΅Π»Π΅Π½Π° ΠΈ Π²ΠΏΠ΅Ρ€Π²Ρ‹Π΅ сиквСнирована ΠΊΠ”ΠΠš Π³Π΅Π½Π° Π΄Π£Π’Π€Π°Π·Ρ‹ ΠΌΡ‹ΡˆΠΈ.

ΠŸΠΎΠΊΠ°Π·Π°Ρ‚ΡŒ вСсь тСкст

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