FBXW 7 regulates a mitochondrial transcription program by modulating MITF
FBXW 7 is well characterized as a tumor suppressor in many human cancers including melanoma; however, the mechanisms of tumor‐suppressive function have not been fully elucidated. We leveraged two distinct RNA sequencing datasets: human melanoma cell lines ( n = 10) with control versus silenced FB...
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| Veröffentlicht in: | Pigment cell and melanoma research 2018-09, Vol.31 (5), p.636-640 |
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| container_title | Pigment cell and melanoma research |
| container_volume | 31 |
| creator | Abbate, Franco Badal, Brateil Mendelson, Karen Aydin, Iraz T. Serasinghe, Madhavika N. Iqbal, Ramiz Mohammed, Jarvier N. Solovyov, Alexander Greenbaum, Benjamin D. Chipuk, Jerry E. Celebi, Julide T. |
| description | FBXW
7 is well characterized as a tumor suppressor in many human cancers including melanoma; however, the mechanisms of tumor‐suppressive function have not been fully elucidated. We leveraged two distinct
RNA
sequencing datasets: human melanoma cell lines (
n
=
10) with control versus silenced
FBXW
7
and a cohort of human melanoma tumor samples (
n
=
51) to define the transcriptomic fingerprint regulated by
FBXW
7. Here, we report that loss of
FBXW
7 enhances a mitochondrial gene transcriptional program that is dependent on
MITF
in human melanoma and confers poor patient outcomes.
MITF
is a lineage‐specific master regulator of melanocytes and together with
PGC
‐1alpha is a marker for melanoma subtypes with dependence for mitochondrial oxidative metabolism. We found that inactivation of
FBXW
7 elevates
MITF
protein levels in melanoma cells. In vitro studies examining loss of
FBXW
7 and
MITF
alone or in combination showed that
FBXW
7 is an upstream regulator for the
MITF
/
PGC
‐1 signaling. |
| doi_str_mv | 10.1111/pcmr.12704 |
| format | Article |
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7 is well characterized as a tumor suppressor in many human cancers including melanoma; however, the mechanisms of tumor‐suppressive function have not been fully elucidated. We leveraged two distinct
RNA
sequencing datasets: human melanoma cell lines (
n
=
10) with control versus silenced
FBXW
7
and a cohort of human melanoma tumor samples (
n
=
51) to define the transcriptomic fingerprint regulated by
FBXW
7. Here, we report that loss of
FBXW
7 enhances a mitochondrial gene transcriptional program that is dependent on
MITF
in human melanoma and confers poor patient outcomes.
MITF
is a lineage‐specific master regulator of melanocytes and together with
PGC
‐1alpha is a marker for melanoma subtypes with dependence for mitochondrial oxidative metabolism. We found that inactivation of
FBXW
7 elevates
MITF
protein levels in melanoma cells. In vitro studies examining loss of
FBXW
7 and
MITF
alone or in combination showed that
FBXW
7 is an upstream regulator for the
MITF
/
PGC
‐1 signaling.</description><identifier>ISSN: 1755-1471</identifier><identifier>EISSN: 1755-148X</identifier><identifier>DOI: 10.1111/pcmr.12704</identifier><language>eng</language><ispartof>Pigment cell and melanoma research, 2018-09, Vol.31 (5), p.636-640</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c764-1975c82813b882dceb96113d47b5fdf0a5acb23c341ad11ab877a4b4b55cb17b3</citedby><cites>FETCH-LOGICAL-c764-1975c82813b882dceb96113d47b5fdf0a5acb23c341ad11ab877a4b4b55cb17b3</cites><orcidid>0000-0001-9926-3780</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Abbate, Franco</creatorcontrib><creatorcontrib>Badal, Brateil</creatorcontrib><creatorcontrib>Mendelson, Karen</creatorcontrib><creatorcontrib>Aydin, Iraz T.</creatorcontrib><creatorcontrib>Serasinghe, Madhavika N.</creatorcontrib><creatorcontrib>Iqbal, Ramiz</creatorcontrib><creatorcontrib>Mohammed, Jarvier N.</creatorcontrib><creatorcontrib>Solovyov, Alexander</creatorcontrib><creatorcontrib>Greenbaum, Benjamin D.</creatorcontrib><creatorcontrib>Chipuk, Jerry E.</creatorcontrib><creatorcontrib>Celebi, Julide T.</creatorcontrib><title>FBXW 7 regulates a mitochondrial transcription program by modulating MITF</title><title>Pigment cell and melanoma research</title><description>FBXW
7 is well characterized as a tumor suppressor in many human cancers including melanoma; however, the mechanisms of tumor‐suppressive function have not been fully elucidated. We leveraged two distinct
RNA
sequencing datasets: human melanoma cell lines (
n
=
10) with control versus silenced
FBXW
7
and a cohort of human melanoma tumor samples (
n
=
51) to define the transcriptomic fingerprint regulated by
FBXW
7. Here, we report that loss of
FBXW
7 enhances a mitochondrial gene transcriptional program that is dependent on
MITF
in human melanoma and confers poor patient outcomes.
MITF
is a lineage‐specific master regulator of melanocytes and together with
PGC
‐1alpha is a marker for melanoma subtypes with dependence for mitochondrial oxidative metabolism. We found that inactivation of
FBXW
7 elevates
MITF
protein levels in melanoma cells. In vitro studies examining loss of
FBXW
7 and
MITF
alone or in combination showed that
FBXW
7 is an upstream regulator for the
MITF
/
PGC
‐1 signaling.</description><issn>1755-1471</issn><issn>1755-148X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNo9kD1PwzAURS0EEqWw8As8I6X4xXbsjFCREqmIJRLdomc7CUb5kh2G_nsoIO5y73LucAi5BbaB79zPdggbSBUTZ2QFSsoEhD6c_28Fl-Qqxg_GMiZzviJl8Xh4o4qGpvvscWkiRTr4ZbLv0-iCx54uAcdog58XP410DlMXcKDmSIfJnRA_dvSlrIprctFiH5ubv16Tqniqts_J_nVXbh_2iVWZSCBX0upUAzdap842Js8AuBPKyNa1DCVak3LLBaADQKOVQmGEkdIaUIavyd3vrQ1TjKFp6zn4AcOxBlafHNQnB_WPA_4FI9VP9w</recordid><startdate>201809</startdate><enddate>201809</enddate><creator>Abbate, Franco</creator><creator>Badal, Brateil</creator><creator>Mendelson, Karen</creator><creator>Aydin, Iraz T.</creator><creator>Serasinghe, Madhavika N.</creator><creator>Iqbal, Ramiz</creator><creator>Mohammed, Jarvier N.</creator><creator>Solovyov, Alexander</creator><creator>Greenbaum, Benjamin D.</creator><creator>Chipuk, Jerry E.</creator><creator>Celebi, Julide T.</creator><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0001-9926-3780</orcidid></search><sort><creationdate>201809</creationdate><title>FBXW 7 regulates a mitochondrial transcription program by modulating MITF</title><author>Abbate, Franco ; Badal, Brateil ; Mendelson, Karen ; Aydin, Iraz T. ; Serasinghe, Madhavika N. ; Iqbal, Ramiz ; Mohammed, Jarvier N. ; Solovyov, Alexander ; Greenbaum, Benjamin D. ; Chipuk, Jerry E. ; Celebi, Julide T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c764-1975c82813b882dceb96113d47b5fdf0a5acb23c341ad11ab877a4b4b55cb17b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abbate, Franco</creatorcontrib><creatorcontrib>Badal, Brateil</creatorcontrib><creatorcontrib>Mendelson, Karen</creatorcontrib><creatorcontrib>Aydin, Iraz T.</creatorcontrib><creatorcontrib>Serasinghe, Madhavika N.</creatorcontrib><creatorcontrib>Iqbal, Ramiz</creatorcontrib><creatorcontrib>Mohammed, Jarvier N.</creatorcontrib><creatorcontrib>Solovyov, Alexander</creatorcontrib><creatorcontrib>Greenbaum, Benjamin D.</creatorcontrib><creatorcontrib>Chipuk, Jerry E.</creatorcontrib><creatorcontrib>Celebi, Julide T.</creatorcontrib><collection>CrossRef</collection><jtitle>Pigment cell and melanoma research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abbate, Franco</au><au>Badal, Brateil</au><au>Mendelson, Karen</au><au>Aydin, Iraz T.</au><au>Serasinghe, Madhavika N.</au><au>Iqbal, Ramiz</au><au>Mohammed, Jarvier N.</au><au>Solovyov, Alexander</au><au>Greenbaum, Benjamin D.</au><au>Chipuk, Jerry E.</au><au>Celebi, Julide T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FBXW 7 regulates a mitochondrial transcription program by modulating MITF</atitle><jtitle>Pigment cell and melanoma research</jtitle><date>2018-09</date><risdate>2018</risdate><volume>31</volume><issue>5</issue><spage>636</spage><epage>640</epage><pages>636-640</pages><issn>1755-1471</issn><eissn>1755-148X</eissn><abstract>FBXW
7 is well characterized as a tumor suppressor in many human cancers including melanoma; however, the mechanisms of tumor‐suppressive function have not been fully elucidated. We leveraged two distinct
RNA
sequencing datasets: human melanoma cell lines (
n
=
10) with control versus silenced
FBXW
7
and a cohort of human melanoma tumor samples (
n
=
51) to define the transcriptomic fingerprint regulated by
FBXW
7. Here, we report that loss of
FBXW
7 enhances a mitochondrial gene transcriptional program that is dependent on
MITF
in human melanoma and confers poor patient outcomes.
MITF
is a lineage‐specific master regulator of melanocytes and together with
PGC
‐1alpha is a marker for melanoma subtypes with dependence for mitochondrial oxidative metabolism. We found that inactivation of
FBXW
7 elevates
MITF
protein levels in melanoma cells. In vitro studies examining loss of
FBXW
7 and
MITF
alone or in combination showed that
FBXW
7 is an upstream regulator for the
MITF
/
PGC
‐1 signaling.</abstract><doi>10.1111/pcmr.12704</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0001-9926-3780</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1755-1471 |
| ispartof | Pigment cell and melanoma research, 2018-09, Vol.31 (5), p.636-640 |
| issn | 1755-1471 1755-148X |
| language | eng |
| recordid | cdi_crossref_primary_10_1111_pcmr_12704 |
| source | Wiley Online Library Journals Frontfile Complete |
| title | FBXW 7 regulates a mitochondrial transcription program by modulating MITF |
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