Sandbox Reserved 1548

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<Structure load='1YZ1' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />
<Structure load='1YZ1' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />
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You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
 
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== Function ==
== Function ==
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TCTP1 is a highly conserved essential anti-apoptotic protein that is known to play a key role in tumor growth. High levels of expression TCTP1 are commonly seen in dividing cells, and it is overexpressed in tumor cells. <ref>PMID:249723495</ref> Decreased expression of TCTP1 in malignant cells has been identified as one possible mechanism of tumor reversion, where tumorgenic cancerous cells cease to be malignant. Specifically, TCTP1 expression is almost undetectable in reverted cells. <ref>DOI10.1038/nm.2546</ref>
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TCTP1 is a highly conserved essential anti-apoptotic protein that is known to play a key role in tumor growth. <ref> 10.1073/pnas.0406776101</ref> High levels of expression TCTP1 are commonly seen in dividing cells, and it is overexpressed in tumor cells. <ref> 10.1073/pnas.0406776101</ref> Decreased expression of TCTP1 in malignant cells has been identified as one possible mechanism of tumor reversion, where tumorgenic cancerous cells cease to be malignant. <ref>DOI10.1038/nm.2546</ref> Specifically, TCTP1 expression is almost undetectable in reverted cells. <ref>DOI10.1038/nm.2546</ref>
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Multiple proposed mechanisms have been proposed to explain TCTP1's ability to help regulate tumorgenic activity. TCTP1 may interact with the pro-apoptotic factor Bax.
 
While many mammals, including humans have one copy of TCTP1, the capybara, the largest rodent has multiple copies of the TCTP1 gene. It is hypothesized that these multiple copies are one mechanism of cell proliferation and growth that enables the capybara to achieve such a large size.
While many mammals, including humans have one copy of TCTP1, the capybara, the largest rodent has multiple copies of the TCTP1 gene. It is hypothesized that these multiple copies are one mechanism of cell proliferation and growth that enables the capybara to achieve such a large size.
== Disease ==
== Disease ==
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High level of TCTP expression in G3-breast tumors is associated with worse clinical outcomes (HR of 8.31 for a distant malignant event and 5.33 for a local re-occurance compared to tumors with low TCTP expression). <ref>DOI10.1038/nm.2546</ref>
== Relevance ==
== Relevance ==
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Multiple proposed mechanisms have been proposed to explain TCTP1's ability to help regulate tumorgenic activity. TCTP1 may interact with the pro-apoptotic factor Bax.
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A second proposed mechanism may be in reciprocal repression with the tumor suppressor p53. <ref>DOI10.1038/nm.2546</ref> Specifically, TCTP may promote p53 degradation by promoting its ubiquitination by MDM2. <ref>DOI10.1038/nm.2546</ref> The specific structural mechanism for this has not been conclusively established.
== Structural highlights ==
== Structural highlights ==
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TCTP has three α helices and nine β strands arranged into two distorted β sheets.
TCTP has three α helices and nine β strands arranged into two distorted β sheets.
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TCTP1 is hypothesized to interact with Bax which has two helices (H5-H6) that are structurally very similar to the H2/H3 in TCTP1.
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TCTP1 is hypothesized to interact with Bax which has two helices (H5-H6) that are structurally very similar to the H2/H3 in TCTP1. It is hypothesized that TCTP1 may be able to interfear with Bax's homodimerization. Site direct mutagenesis of two key residues (E102 and K109) results in increased apoptosis.
<scene name='80/806434/Mutations_e102_k109/1'>E102 and K109 residues are critical for TCTP1's anti-apoptotic activity</scene>
<scene name='80/806434/Mutations_e102_k109/1'>E102 and K109 residues are critical for TCTP1's anti-apoptotic activity</scene>

Revision as of 17:44, 29 April 2019

This Sandbox is Reserved from May 28 through July 01, 2019 for use in the course Advanced Biochemistry BCHM 4100 taught by Tom Gluick at the Georgia Gwinnett College. This reservation includes Sandbox Reserved 1544 through Sandbox Reserved 1555.
To get started:
  • Click the edit this page tab at the top. Save the page after each step, then edit it again.
  • Click the 3D button (when editing, above the wikitext box) to insert Jmol.
  • show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page.
  • Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc.

More help: Help:Editing

Contents

Transitionally controlled tumor protein 1 (TCTP1/TPT1)

Insert caption here

Drag the structure with the mouse to rotate

Function

TCTP1 is a highly conserved essential anti-apoptotic protein that is known to play a key role in tumor growth. [1] High levels of expression TCTP1 are commonly seen in dividing cells, and it is overexpressed in tumor cells. [2] Decreased expression of TCTP1 in malignant cells has been identified as one possible mechanism of tumor reversion, where tumorgenic cancerous cells cease to be malignant. [3] Specifically, TCTP1 expression is almost undetectable in reverted cells. [4]


While many mammals, including humans have one copy of TCTP1, the capybara, the largest rodent has multiple copies of the TCTP1 gene. It is hypothesized that these multiple copies are one mechanism of cell proliferation and growth that enables the capybara to achieve such a large size.

Disease

High level of TCTP expression in G3-breast tumors is associated with worse clinical outcomes (HR of 8.31 for a distant malignant event and 5.33 for a local re-occurance compared to tumors with low TCTP expression). [5]

Relevance

Multiple proposed mechanisms have been proposed to explain TCTP1's ability to help regulate tumorgenic activity. TCTP1 may interact with the pro-apoptotic factor Bax.

A second proposed mechanism may be in reciprocal repression with the tumor suppressor p53. [6] Specifically, TCTP may promote p53 degradation by promoting its ubiquitination by MDM2. [7] The specific structural mechanism for this has not been conclusively established.

Structural highlights

TCTP has three α helices and nine β strands arranged into two distorted β sheets.

TCTP1 is hypothesized to interact with Bax which has two helices (H5-H6) that are structurally very similar to the H2/H3 in TCTP1. It is hypothesized that TCTP1 may be able to interfear with Bax's homodimerization. Site direct mutagenesis of two key residues (E102 and K109) results in increased apoptosis.

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>

References

  1. ↑ 10.1073/pnas.0406776101
  2. ↑ 10.1073/pnas.0406776101
  3. ↑ . PMID:216315890657
  4. ↑ . PMID:216315890657
  5. ↑ . PMID:216315890657
  6. ↑ . PMID:216315890657
  7. ↑ . PMID:216315890657
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