Functional Role of Cyclin-Dependent Kinase 5 in the Regulation of Melanogenesis and Epidermal Structure
The mammalian integumentary system plays important roles in body homeostasis, and dysfunction of melanogenesis or epidermal development may lead to a variety of skin diseases, including melanoma. Skin pigmentation in humans and coat color in fleece-producing animals are regulated by many genes. Amon...
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| Veröffentlicht in: | Scientific reports 2017-10, Vol.7 (1), p.13783-12, Article 13783 |
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| creator | Dong, Changsheng Yang, Shanshan Fan, Ruiwen Ji, Kaiyuan Zhang, Junzhen Liu, Xuexian Hu, Shuaipeng Xie, Jianshan Liu, Yu Gao, Wenjun Wang, Haidong Yao, Jianbo Smith, George W Herrid, Muren |
| description | The mammalian integumentary system plays important roles in body homeostasis, and dysfunction of melanogenesis or epidermal development may lead to a variety of skin diseases, including melanoma. Skin pigmentation in humans and coat color in fleece-producing animals are regulated by many genes. Among them, microphthalmia-associated transcription factor (
MITF
) and paired-box 3 (
PAX3
) are at the top of the cascade and regulate activities of many important melanogenic enzymes. Here, we report for the first time that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of
MITF
and
PAX3
.
Cdk5
knockdown in mice causes a lightened coat color, a polarized distribution of melanin and hyperproliferation of basal keratinocytes. Reduced expression of Keratin 10 (
K10
) resulting from
Cdk5
knockdown may be responsible for an abnormal epidermal structure. In contrast, overexpression of
Cdk5
in sheep (Ovis aries) only produces brown patches on a white background, with no other observable abnormalities. Collectively, our findings show that Cdk5 has an important functional role in the regulation of melanin production and transportation and in normal development of the integumentary system. |
| doi_str_mv | 10.1038/s41598-017-12567-1 |
| format | Article |
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MITF
) and paired-box 3 (
PAX3
) are at the top of the cascade and regulate activities of many important melanogenic enzymes. Here, we report for the first time that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of
MITF
and
PAX3
.
Cdk5
knockdown in mice causes a lightened coat color, a polarized distribution of melanin and hyperproliferation of basal keratinocytes. Reduced expression of Keratin 10 (
K10
) resulting from
Cdk5
knockdown may be responsible for an abnormal epidermal structure. In contrast, overexpression of
Cdk5
in sheep (Ovis aries) only produces brown patches on a white background, with no other observable abnormalities. Collectively, our findings show that Cdk5 has an important functional role in the regulation of melanin production and transportation and in normal development of the integumentary system.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-017-12567-1</identifier><identifier>PMID: 29062096</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/109 ; 13/89 ; 14 ; 38 ; 42 ; 631/1647/2017 ; 631/61/191/505 ; Animals ; Cells, Cultured ; Coloration ; Cyclin-dependent kinase 5 ; Cyclin-Dependent Kinase 5 - genetics ; Cyclin-Dependent Kinase 5 - metabolism ; Cyclin-dependent kinases ; Down-Regulation ; Epidermis - chemistry ; Epidermis - growth & development ; Epidermis - metabolism ; Female ; Homeostasis ; Humanities and Social Sciences ; Keratin ; Keratinocytes ; Male ; Melanin ; Melanocytes - cytology ; Melanocytes - metabolism ; Melanoma ; Mice ; Mice, Knockout ; Microphthalmia-associated transcription factor ; multidisciplinary ; Ovis aries ; Pax3 protein ; Pigmentation ; Science ; Science (multidisciplinary) ; Sheep ; Signal Transduction ; Skin diseases ; Skin pigmentation ; Skin Pigmentation - physiology</subject><ispartof>Scientific reports, 2017-10, Vol.7 (1), p.13783-12, Article 13783</ispartof><rights>The Author(s) 2017</rights><rights>2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-7700b68427051f9fe1326b0c68687020a58f05192445ca3edf8d90b01b1373093</citedby><cites>FETCH-LOGICAL-c474t-7700b68427051f9fe1326b0c68687020a58f05192445ca3edf8d90b01b1373093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5653820/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5653820/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29062096$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dong, Changsheng</creatorcontrib><creatorcontrib>Yang, Shanshan</creatorcontrib><creatorcontrib>Fan, Ruiwen</creatorcontrib><creatorcontrib>Ji, Kaiyuan</creatorcontrib><creatorcontrib>Zhang, Junzhen</creatorcontrib><creatorcontrib>Liu, Xuexian</creatorcontrib><creatorcontrib>Hu, Shuaipeng</creatorcontrib><creatorcontrib>Xie, Jianshan</creatorcontrib><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Gao, Wenjun</creatorcontrib><creatorcontrib>Wang, Haidong</creatorcontrib><creatorcontrib>Yao, Jianbo</creatorcontrib><creatorcontrib>Smith, George W</creatorcontrib><creatorcontrib>Herrid, Muren</creatorcontrib><title>Functional Role of Cyclin-Dependent Kinase 5 in the Regulation of Melanogenesis and Epidermal Structure</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The mammalian integumentary system plays important roles in body homeostasis, and dysfunction of melanogenesis or epidermal development may lead to a variety of skin diseases, including melanoma. Skin pigmentation in humans and coat color in fleece-producing animals are regulated by many genes. Among them, microphthalmia-associated transcription factor (
MITF
) and paired-box 3 (
PAX3
) are at the top of the cascade and regulate activities of many important melanogenic enzymes. Here, we report for the first time that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of
MITF
and
PAX3
.
Cdk5
knockdown in mice causes a lightened coat color, a polarized distribution of melanin and hyperproliferation of basal keratinocytes. Reduced expression of Keratin 10 (
K10
) resulting from
Cdk5
knockdown may be responsible for an abnormal epidermal structure. In contrast, overexpression of
Cdk5
in sheep (Ovis aries) only produces brown patches on a white background, with no other observable abnormalities. Collectively, our findings show that Cdk5 has an important functional role in the regulation of melanin production and transportation and in normal development of the integumentary system.</description><subject>13/109</subject><subject>13/89</subject><subject>14</subject><subject>38</subject><subject>42</subject><subject>631/1647/2017</subject><subject>631/61/191/505</subject><subject>Animals</subject><subject>Cells, Cultured</subject><subject>Coloration</subject><subject>Cyclin-dependent kinase 5</subject><subject>Cyclin-Dependent Kinase 5 - genetics</subject><subject>Cyclin-Dependent Kinase 5 - metabolism</subject><subject>Cyclin-dependent kinases</subject><subject>Down-Regulation</subject><subject>Epidermis - chemistry</subject><subject>Epidermis - growth & development</subject><subject>Epidermis - metabolism</subject><subject>Female</subject><subject>Homeostasis</subject><subject>Humanities and Social Sciences</subject><subject>Keratin</subject><subject>Keratinocytes</subject><subject>Male</subject><subject>Melanin</subject><subject>Melanocytes - cytology</subject><subject>Melanocytes - metabolism</subject><subject>Melanoma</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Microphthalmia-associated transcription factor</subject><subject>multidisciplinary</subject><subject>Ovis aries</subject><subject>Pax3 protein</subject><subject>Pigmentation</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Sheep</subject><subject>Signal Transduction</subject><subject>Skin diseases</subject><subject>Skin pigmentation</subject><subject>Skin Pigmentation - physiology</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kU1rFTEUhoNYbKn9Ay4k4MbN1JOvmWQjyLW1Ykuh1XXIzJyZpsxNrsmM0H9vbm8tV8EsksB5zns-XkLeMDhlIPSHLJkyugLWVIyrutwvyBEHqSouOH-59z8kJznfQzmKG8nMK3LIDdQcTH1ExvMldLOPwU30Jk5I40BXD93kQ_UZNxh6DDP95oPLSBX1gc53SG9wXCa3zdriVzi5EEcMmH2mLvT0bON7TOsieTunpZuXhK_JweCmjCdP7zH5cX72fXVRXV5_-br6dFl1spFz1TQAba0lb0CxwQzIBK9b6Gpd6wY4OKWHEjFcStU5gf2gewMtsJaJRoARx-TjTneztGvsu9J-cpPdJL926cFG5-3fkeDv7Bh_WVUroTkUgfdPAin-XDDPdu1zh1OZEeOSLTNKleVJYAV99w96H5dUNvlISaGFZk2h-I7qUsw54fDcDAO7tdLurLTFSvtopd1Kv90f4znlj3EFEDsgl1AYMe3V_r_sb7ntqHk</recordid><startdate>20171023</startdate><enddate>20171023</enddate><creator>Dong, Changsheng</creator><creator>Yang, Shanshan</creator><creator>Fan, Ruiwen</creator><creator>Ji, Kaiyuan</creator><creator>Zhang, Junzhen</creator><creator>Liu, Xuexian</creator><creator>Hu, Shuaipeng</creator><creator>Xie, Jianshan</creator><creator>Liu, Yu</creator><creator>Gao, Wenjun</creator><creator>Wang, Haidong</creator><creator>Yao, Jianbo</creator><creator>Smith, George W</creator><creator>Herrid, Muren</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20171023</creationdate><title>Functional Role of Cyclin-Dependent Kinase 5 in the Regulation of Melanogenesis and Epidermal Structure</title><author>Dong, Changsheng ; Yang, Shanshan ; Fan, Ruiwen ; Ji, Kaiyuan ; Zhang, Junzhen ; Liu, Xuexian ; Hu, Shuaipeng ; Xie, Jianshan ; Liu, Yu ; Gao, Wenjun ; Wang, Haidong ; Yao, Jianbo ; Smith, George W ; Herrid, Muren</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-7700b68427051f9fe1326b0c68687020a58f05192445ca3edf8d90b01b1373093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>13/109</topic><topic>13/89</topic><topic>14</topic><topic>38</topic><topic>42</topic><topic>631/1647/2017</topic><topic>631/61/191/505</topic><topic>Animals</topic><topic>Cells, Cultured</topic><topic>Coloration</topic><topic>Cyclin-dependent kinase 5</topic><topic>Cyclin-Dependent Kinase 5 - genetics</topic><topic>Cyclin-Dependent Kinase 5 - metabolism</topic><topic>Cyclin-dependent kinases</topic><topic>Down-Regulation</topic><topic>Epidermis - chemistry</topic><topic>Epidermis - growth & development</topic><topic>Epidermis - metabolism</topic><topic>Female</topic><topic>Homeostasis</topic><topic>Humanities and Social Sciences</topic><topic>Keratin</topic><topic>Keratinocytes</topic><topic>Male</topic><topic>Melanin</topic><topic>Melanocytes - cytology</topic><topic>Melanocytes - metabolism</topic><topic>Melanoma</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Microphthalmia-associated transcription factor</topic><topic>multidisciplinary</topic><topic>Ovis aries</topic><topic>Pax3 protein</topic><topic>Pigmentation</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Sheep</topic><topic>Signal Transduction</topic><topic>Skin diseases</topic><topic>Skin pigmentation</topic><topic>Skin Pigmentation - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dong, Changsheng</creatorcontrib><creatorcontrib>Yang, Shanshan</creatorcontrib><creatorcontrib>Fan, Ruiwen</creatorcontrib><creatorcontrib>Ji, Kaiyuan</creatorcontrib><creatorcontrib>Zhang, Junzhen</creatorcontrib><creatorcontrib>Liu, Xuexian</creatorcontrib><creatorcontrib>Hu, Shuaipeng</creatorcontrib><creatorcontrib>Xie, Jianshan</creatorcontrib><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Gao, Wenjun</creatorcontrib><creatorcontrib>Wang, Haidong</creatorcontrib><creatorcontrib>Yao, Jianbo</creatorcontrib><creatorcontrib>Smith, George W</creatorcontrib><creatorcontrib>Herrid, Muren</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dong, Changsheng</au><au>Yang, Shanshan</au><au>Fan, Ruiwen</au><au>Ji, Kaiyuan</au><au>Zhang, Junzhen</au><au>Liu, Xuexian</au><au>Hu, Shuaipeng</au><au>Xie, Jianshan</au><au>Liu, Yu</au><au>Gao, Wenjun</au><au>Wang, Haidong</au><au>Yao, Jianbo</au><au>Smith, George W</au><au>Herrid, Muren</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional Role of Cyclin-Dependent Kinase 5 in the Regulation of Melanogenesis and Epidermal Structure</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-10-23</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>13783</spage><epage>12</epage><pages>13783-12</pages><artnum>13783</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The mammalian integumentary system plays important roles in body homeostasis, and dysfunction of melanogenesis or epidermal development may lead to a variety of skin diseases, including melanoma. Skin pigmentation in humans and coat color in fleece-producing animals are regulated by many genes. Among them, microphthalmia-associated transcription factor (
MITF
) and paired-box 3 (
PAX3
) are at the top of the cascade and regulate activities of many important melanogenic enzymes. Here, we report for the first time that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of
MITF
and
PAX3
.
Cdk5
knockdown in mice causes a lightened coat color, a polarized distribution of melanin and hyperproliferation of basal keratinocytes. Reduced expression of Keratin 10 (
K10
) resulting from
Cdk5
knockdown may be responsible for an abnormal epidermal structure. In contrast, overexpression of
Cdk5
in sheep (Ovis aries) only produces brown patches on a white background, with no other observable abnormalities. Collectively, our findings show that Cdk5 has an important functional role in the regulation of melanin production and transportation and in normal development of the integumentary system.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29062096</pmid><doi>10.1038/s41598-017-12567-1</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Springer Nature OA/Free Journals; Free Full-Text Journals in Chemistry |
| subjects | 13/109 13/89 14 38 42 631/1647/2017 631/61/191/505 Animals Cells, Cultured Coloration Cyclin-dependent kinase 5 Cyclin-Dependent Kinase 5 - genetics Cyclin-Dependent Kinase 5 - metabolism Cyclin-dependent kinases Down-Regulation Epidermis - chemistry Epidermis - growth & development Epidermis - metabolism Female Homeostasis Humanities and Social Sciences Keratin Keratinocytes Male Melanin Melanocytes - cytology Melanocytes - metabolism Melanoma Mice Mice, Knockout Microphthalmia-associated transcription factor multidisciplinary Ovis aries Pax3 protein Pigmentation Science Science (multidisciplinary) Sheep Signal Transduction Skin diseases Skin pigmentation Skin Pigmentation - physiology |
| title | Functional Role of Cyclin-Dependent Kinase 5 in the Regulation of Melanogenesis and Epidermal Structure |
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